BACKGROUND The research findings suggest that the prognosis of children with Wilms tumor(WT)is affected by various factors.Some scholars have indicated that loss of heterozygosity(LOH)on chromosome 16q is associated w...BACKGROUND The research findings suggest that the prognosis of children with Wilms tumor(WT)is affected by various factors.Some scholars have indicated that loss of heterozygosity(LOH)on chromosome 16q is associated with a poor prognosis in patients with WT.AIM To further elucidate this relationship,we conducted a meta-analysis.METHODS This meta-analysis was registered in INPLASY(INPLASY2023100060).We systematically searched databases including Embase,PubMed,Web of Science,Cochrane,and Google Scholar up to May 31,2020,for randomized trials reporting any intrapartum fetal surveillance approach.The meta-analysis was performed within a frequentist framework,and the quality and network inconsistency of trials were assessed.Odds ratios and 95%CIs were calculated to report the relationship between event-free survival and 16q LOH in patients with WT.RESULTS Eleven cohort studies were included in this meta-analysis to estimate the relationship between event-free survival and 16q LOH in patients with WT(I^(2)=25%,P<0.001).As expected,16q LOH can serve as an effective predictor of eventfree survival in patients with WT(risk ratio=1.95,95%CI:1.52–2.49,P<0.001).CONCLUSION In pediatric patients with WT,there exists a partial correlation between 16q LOH and an unfavorable treatment prognosis.Clinical detection of 16q chromosome LOH warrants increased attention to the patient’s prognosis.展开更多
AIM To correlate the length of the telomere to microsatellite instability (MSI) and loss of heterozygosity (LOH) of APC, MCC and DCC genes in gastric carcinomas.METHODS Telomeric restriction fragment (TRF) length of g...AIM To correlate the length of the telomere to microsatellite instability (MSI) and loss of heterozygosity (LOH) of APC, MCC and DCC genes in gastric carcinomas.METHODS Telomeric restriction fragment (TRF) length of gastric cancer was measured with Southern blot. LOH of APC, MCC and DCC genes, microsatellite instability (MSI) and frameshift mutation of hMSH6, TGF-βR Ⅱ and BAX genes were analyzed by PCR-based methods.RESULTS Sixty-eight cases of sporadic gastric carcinoma were studied for MSI using five microsatellite markers. MSI in at least one locus was detected in 17 (25%) of 68 tumors analyzed. Frameshift mutations of hMSH6, TGF-βR Ⅱ and BAX were detected in 2,6 and 3 of gastric carcinomas respectively showing high MSI (≥ 2 loci, n = 8), but none was found in those showing Iow MSI (only one locus, n = 9) or MSS (tumor lacking MSI or stable, n = 51). Thirty-five cases, including all high MSI and Iow MSl, were studied for TRF. The mean TRF length was not correlated with clinicopathological parameters.No association was observed between TRF length and MSI or frameshift mutation. On the contrary, LOH at the DCC locus was related to telomere shortening (P< 0.01). This tendency was also observed in APC and MCC genes,although there was no statistical significance.CONCLUSION The development of gastric cancer can arise through two different genetic pathways. In high MSI gastric cancers, defective mismatch repair allows mutations to accumulate and generate the high MSI phenotype. In gastric cancers showing either Iow MSI or MSS, multiple deletions may represent the LOH pathway.Telomere erosion is independent of high MSI phenotype but related to the LOH pathway in gastric cancer.展开更多
To elucidate the molecular pathology underlying the development of hepatocellular carcinoma (HCC), we used 41 highly polymorphic microsatellite markers to examine 55 HCC and corresponding non-tumor liver tissues on ch...To elucidate the molecular pathology underlying the development of hepatocellular carcinoma (HCC), we used 41 highly polymorphic microsatellite markers to examine 55 HCC and corresponding non-tumor liver tissues on chromosome 9, 16 and 17. Loss-of-heterozygosity (LOH) is observed with high frequency on chromosomal region 17p13 (36/55, 65%), 9p21-p23 (28/55, 51%), 16q21-q23 (27/55, 49%) in tumors. Meanwhile, microsatellite instability is rarely found in these microsatellite loci. Direct sequencing was performed to detect the tentative mutation of tumor suppressor genes in these regions: p53, MTS1/p16, and CDH1/E-cadherin. Within exon 5-9 of p53 gene, 14 out of 55 HCC specimens (24%) have somatic mutations, and nucleotide deletion of this gene is reported in HCC for the first time. Mutation in MTS1/pl6 is found only in one tumor case. We do not find mutations in CDH1/E-cadherin. Furthermore, a statistically significant correlation is present between p53 gene mutation and loss of chromosome region 16q21q23 and 9p21-p23, which indicates that synergism between p53 inactivation and deletion of 16q21-q23 and 9p21-p23 may play a role in the pathogenesis of HCC. Genetic aberration in hepatocellular展开更多
To investigate the correlation of individual heterozygosity and heterosis of three traits in crossbred F1 pig populations, the F1 populations were built by random mating Yorkshire x Meishan (YM, n = 82), and its rec...To investigate the correlation of individual heterozygosity and heterosis of three traits in crossbred F1 pig populations, the F1 populations were built by random mating Yorkshire x Meishan (YM, n = 82), and its reciprocal (MY, n =47) and two straightbred populations (Yorkshire = 34, Meishan = 55) were used as control groups. The heterosis of birth weight (BWT), average daily gain (ADG), and feed conversion ratio (FCR) were acquired as well. In the research, the significant marker loci for the heterosis of the three traits were observed by one-way ANOVA (P〈0.01) in a total of 39 marker loci on SSC4, SSC6, SSC7, SSC8, and SSC13, and the numbers of the significant marker loci were 12 (BWT), 18 (ADG), and 17 (FCR), respectively, based on which the general heterozygosity (GH) was divided into significant marker loci heterozygosity (SH) and insignificant marker loci heterozygosity (IH). Furthermore, the trends of alteration in heterosis with the stepwise increase in heterozygosity by 0.05 were explored. This was done by the regression analysis of the three kinds of heterozygosity against heterosis of the three traits. The results showed that, for BWT, the heterosis increased with the increase in GH (r=0.9337, P=0.0021) and SH (r=0.9165, P=0.0102); for ADG, the heterosis increased with the increase in IH (r=0.7012, P=0.0353) and GH (r=0.7470, P=0.0537, near significant); for FCR, the heterosis of feed efficiency increased with the increase in IH (r=0.8721, P=0.0022). The results indicated that the correlation was not always higher or more significant for SH with heterosis than it was for IH or GH with heterosis, and it might be because of the reciprocal cancellation of the positive effect and negative effect of QTL linked to the significant marker loci.展开更多
Oligodendroglial tumors frequently have deletions ofchromosomal loci on lp and l9q.Loas of heterozygosity(LOH)of chromosome 10 may be a negative prognostic factor.We reviewed 23 patients with oligodendroglial tumors,t...Oligodendroglial tumors frequently have deletions ofchromosomal loci on lp and l9q.Loas of heterozygosity(LOH)of chromosome 10 may be a negative prognostic factor.We reviewed 23 patients with oligodendroglial tumors,toevaluate the frequency of lp and 10q LOH and correlate with clinical outcome.Three loci(DlS402,DlSl 172,MCT118)on lp and 2 loci(Dl0S520 and D10S521)on 10q were analyzed for LOH using PCR techniques.展开更多
Objective: To analysis the chromosome 8 heterozygosity loss in human prostate carcinoma and high grade prostatic intraepithelial neoplasia. Methods: Pure DNA was obtained from prostate neoplasms and normal tissues by ...Objective: To analysis the chromosome 8 heterozygosity loss in human prostate carcinoma and high grade prostatic intraepithelial neoplasia. Methods: Pure DNA was obtained from prostate neoplasms and normal tissues by tissue microdissection. The chromosome 8 heterozygosity loss was detected by PCR based micro-satellite polymorphism analysis technique using 14 pairs of microsatellite primers in 10 samples of prostate carcinoma and 10 samples of high grade prostatic intraepithelial neoplasia. Results: There were different frequencies of chromosome 8 heterozygosity loss in 10 samples of prostate carcinoma. 8p23.1-p23.2 and p21-p22 were two high frequency heterozygosity loss regions. Chromosome 8 heterozygosity loss was detected in 3 samples of high grade prostatic intraepithelial neoplasia. Conclusion: There were high frequency heterozygosity loss regions on chromosome 8 of prostate carcinoma, located at 8p23.1-p23.2 and p21-p22. The high grade prostatic intraepithelial neoplasia and prostate carcinoma share the same allelic loss on 8p. Tumor suppressor genes located at these two regions may be potentially involved in the initiation and progression of prostate carcinoma.展开更多
Objective: Clinically, the reason of resistance for breast cancer to endocrine therapy has not been well known. The current study attempted to examine loss of heterozygosity (LOH) on the estrogen receptor (ER) gene in...Objective: Clinically, the reason of resistance for breast cancer to endocrine therapy has not been well known. The current study attempted to examine loss of heterozygosity (LOH) on the estrogen receptor (ER) gene in breast cancer and its relationship to clinicopathologic findings. Methods: DNAs of tumor tissues and blood lymphocytes were collected from 40 cases of primary breast cancer patients and LOH were detected using the microsatellite repeat assay and combined with other ER immunohistochemical assays. Results: ER-positive staining was observed in 65% of breast cancer. Heterogeneity of ER expression was found. Seven of the patients (17.5%) showed LOH. In three of the seven cases, there was total loss, and there was a marked reduction in the intensity of signal in the other four cases. LOH was associated with histologic grade, occurring more frequently in ER-negative and lymph node metastasis group, but not with tumor size and patient ages. Conclusion: This result implied that LOH of the ER gene may have an important role in the progression of breast cancer. It was postulated that the lack of ER function induced by LOH may contributed to endocrine therapy resistance of breast cancer since the tumor clone would escape from the ER regulation, obtain growth predisposition and finally lost response to therapy.展开更多
Southern hybridization was done on DNA samples of22 gastric tumors and corresponding normal tissues, 14colorectal tumors and corresponding normal tissues by probe phs53B mapping at 17P13.1 and probe PYNZ22mapping at 1...Southern hybridization was done on DNA samples of22 gastric tumors and corresponding normal tissues, 14colorectal tumors and corresponding normal tissues by probe phs53B mapping at 17P13.1 and probe PYNZ22mapping at 17pl3.3 which were purchased from the American Type Culture Collection. RFLP heterozygosity was observed in 12 normal tissues of gastric cancers and 10 normal tissues of colorectal cancers. Among these informative tumors, 6(50%) cases of gastric cancers and 6(60%) cases of colorectal cancers showed the loss of beterozygosity at 17p13. Our results demonstrated that the inactivation of wild type p53 might be involved in the carcinogenesis of gastric cancers and colorectal cancers.Furthermore, the mode of inactivation of p53 was in accord with the 'two hits' hypothesis by Anudson. The signincance was discussed regarding the presence of LOH detected by probe PYNZ22 mapping at 17pl3.3.展开更多
To investigate whether aberration of the APC gene play any role in the development of Chinese sporadic colorectal carcinomas,we used a polymorphic site located in exon 11 which creted a new restriction site for RsaI t...To investigate whether aberration of the APC gene play any role in the development of Chinese sporadic colorectal carcinomas,we used a polymorphic site located in exon 11 which creted a new restriction site for RsaI to analyze LOH for the APC gene.We found that 20/29(68.9%) patients with colorectal cancer were informative for the APC exon 11 site and loss of one allele was detected in 40% of 20 informativc cascs.These data suggested that loss of heterozygosity of APC gene(APC-LOH) play a role in the pathogenesis of Chinese colorectal cancer.APC-LOH is a earlier event of colorectal tumorigenesis and may be of diagnostic value in Patient suffering colorectal cancer.展开更多
Objective To analyze the loss of heterozygosity (LOH) for markers on chromosew 22 (CHR 22 ) and its significance with their clinical behaviors. Methods The frequency of CHR22 LOH in 36 schwannomas was observed by dena...Objective To analyze the loss of heterozygosity (LOH) for markers on chromosew 22 (CHR 22 ) and its significance with their clinical behaviors. Methods The frequency of CHR22 LOH in 36 schwannomas was observed by denatured polyacrylamide gels and silver staining, and the proliferative index of schwannoma wes calculated by Ki-67 and PCNA immunohistochemistry. Results 15 schwannomas (41. 6% ) shawed allele lass. The proliferative index of schwannomas with LOH were significantly higher than those without LOH (P< 0. 05). In acoustic neuromas, patients with LOH were younger at the age of diagnosis, larger size of tumor, shorter history and higher growth rate than those without LOH, but with no significance. Conclusion CHR22 IDH was the frequent event in the tumorigenesis of sporadic schwannoma. There were some links beteen CHR22 LOH and clinical behavior.展开更多
function.FHIT is a potential tumor suppressor gene.Although the precise FHIT molecular mechanism of action is not well understood,evidences suggest that Fhit protein reduced levels are involved in mammary carcinogenes...function.FHIT is a potential tumor suppressor gene.Although the precise FHIT molecular mechanism of action is not well understood,evidences suggest that Fhit protein reduced levels are involved in mammary carcinogenesis.The aim of this study was to investigate if FHIT LOH could influence on sporadic breast cancer(BC)biological behavior,through its association with prognostic factors for sporadic BC.Tumor tissue and peripheral blood samples were analyzed using the microsatellite marker D3S1300.The findings were associated with clinicopathological parameters including overall survival.LOH was detected in 31.1%(52/167)of the informative BC’cases.Considering clinical and pathological characteristics we have found no significant association with FHIT LOH status.The mean follow-up time was 80 months.After the Cox regression analysis two parameters remained associated with BC’s risk of death:TNM stage III and IV-HR=3.74(95%CI,1.16-12.1)P=0.027 and disease relapse HR=3.14(CI 95%1.26-7.80)P=0.014.This study shows that FHIT LOH by itself is not a prognostic factor for sporadic BC.Further researches are required to elucidate the functional role of FHIT LOH concerning to BC.展开更多
Germ cell tumors complicated by hematological malignancy(HM)are a rare clinical phenomenon.Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is a potentially effective therapy,but graft-versus-host disease(...Germ cell tumors complicated by hematological malignancy(HM)are a rare clinical phenomenon.Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is a potentially effective therapy,but graft-versus-host disease(GVHD)is a life-threatening complication.We report a case of a 13-year-old female patient diagnosed with germ cell tumors followed by acute lymphoblastic leukemia.After chemotherapy,she received allo-HSCT and her chimerism rate decreased rapidly to near zero by 6 months without evidence of HM recurrence.However,she developed severe,multiorgan GVHD-like manifestations.DNA analysis revealed the pathogenesis of GVHD to be loss of HLA heterozygosity in recipient hematopoietic cells.展开更多
Genetic variation drives phenotypic evolution within populations. Genetic variation can be divided into different forms according to the size of genomic changes. However, study of large-scale genomic variation such as...Genetic variation drives phenotypic evolution within populations. Genetic variation can be divided into different forms according to the size of genomic changes. However, study of large-scale genomic variation such as structural variation and aneuploidy is still limited and mainly based on the static, predetermined feature of individual genomes. Here, using SCRaMbLE,different levels of loss of heterozygosity(LOH) events including short-range LOH, long-range LOH and whole chromosome LOH were detected in evolved strains. By contrast, using rapid adaptive evolution, aneuploidy was detected in the adaptive strains. It was further found that deletion of gene GLN3, long-range LOH in the left arm of synthetic chromosome Ⅹ, whole chromosome LOH of synthetic chromosome Ⅹ, and duplication of chromosome Ⅷ(trisomy) lead to increased rapamycin resistance in synthetic yeast. Comparative analysis of genome stability of evolved strains indicates that the aneuploid strain has a higher frequency of degeneration than the SCRaMbLEd strain. These findings enrich our understanding of genetic mechanism of rapamycin resistance in yeast, and provide valuable insights into yeast genome architecture and function.展开更多
Background Schwannoma is the tumor arising mainly from the cranial and spinal nerves. Bilateral vestibular schwannoma is the hallmark of neurofibromatosis type 2 (NF2). The NF2 gene has been cloned with comprehensiv...Background Schwannoma is the tumor arising mainly from the cranial and spinal nerves. Bilateral vestibular schwannoma is the hallmark of neurofibromatosis type 2 (NF2). The NF2 gene has been cloned with comprehensive analysis of its mutations in schwannoma. However, most studies focused on vestibular schwannoma. There are differences in proliferation of tumor cell and uhrastructure between vestibular and spinal schwannomas. It is unknown whether genetic alterations in vestibular schwannoma are different from those in non-vestibular schwannoma. We analyzed the loss of heterozygosity (LOH) on chromosome 22 in patients with sporadic schwannoma including vestibular and spinal schwannomas and correlated this genetic alteration with tumor proliferation. Methods In 54 unrelated patients without clinical NF1 or NF2, 36 patients had sporadic vestibular schwannoma, and 18 dorsal spinal root schwannoma. Four highly polymorphic linkage to NF2 gene microsatellite DNA markers (D22S264, D22S268, D22S280, CRYB2) were used to analyze LOH. The proliferative index was evaluated by Ki-67 and proliferative cell nuclear antigen (PCNA) immunostaining. Student's t test was used to analyze the difference of the proliferative index between schwannoma with LOH and that without LOH. The difference of the frequency of LOH in vestibular and spinal schwannomas was investigated by the chi-square test. Results Twenty-three schwannomas (42. 6% , 23/54) showed allele loss. The frequency of LOH in vestibular schwannoma was significantly higher than that in spinal schwannoma ( X^2 = 5.14, P 〈 0.05 ). The proliferative index of schwannoma with LOH was significantly higher than that without LOH (tki-67 = 2. 97, P= 0. 0045 ; tPCNA =2.93, P =0. 0051). Conclusions LOH on chromosome 22 is a frequent there is a correlation between LOH on chromosome 22 event in the tumorigenesis of sporadic schwannoma. And, and proliferative activity in schwannoma. The frequency of LOH in vestibular schwannoma is significantly different from that in spinal schwannoma.展开更多
To further illustrate the roles of p53 gene, epidermal growth factor receptor (EGFR) gene and loss of heterozygosity (LOH) on chromosome 10 and 17?p in human glioma progression Methods p53 mutations were scann...To further illustrate the roles of p53 gene, epidermal growth factor receptor (EGFR) gene and loss of heterozygosity (LOH) on chromosome 10 and 17?p in human glioma progression Methods p53 mutations were scanned in 50 gliomas with various malignant grades using the polymerase chain reaction single strand conformation polymorphism (PCR SSCP) assay, and were confirmed by direct sequencing LOH for chromosome 10, 17?p and amplification of the EGFR gene were also assessed using Southern blot analysis Results p53 mutations were found in 9 of 17 high grade astrocytomas (53%), 1 of 15 low grade astrocytomas (7%), and the only subject of eppendymoblastoma but in none of the 10 medulloblastomas and 7 eppendymomas The majority of gliomas (38/50) analyzed here retained both 17?p alleles The frequency of p53 mutations was 13% in this group of tumors and increased to 50% (6/12) in tumors with one 17?p allele ( P <0 025) LOH on chromosome 10 was found in 35% (6/17) of high grade astrocytomas, in 10% (1/10) of medulloblastomas, but in 0% of low grade gliomas EGFR gene amplification was found in 9 high grade gliomas, 60% (6/9) of which also presented LOH for chromosome 10 Conclusions These results indicate that p53 inactivation is a common genetic event in astrocytoma progression that may be more strongly associated with the progression of astrocytomas than with their origin Absence of p53 mutations in 50% of the tumors with one 17?p allele suggests that a tumor suppressor gene other than p53 may be located on chromosome 17?p and involved in progression to malignancy of some gliomas The loss of alleles on chromosome 10 and the amplification of the EGFR gene appear to be restricted to high grade tumors, suggesting that these events may be related to tumor progression rather than initiation展开更多
Background This study was designed to investigate the hot spots of microsatellite loss of heterozygosity (LOH) on 9p13-23 in laryngeal squamous cell carcinoma and to find out the correlation between the incidence of ...Background This study was designed to investigate the hot spots of microsatellite loss of heterozygosity (LOH) on 9p13-23 in laryngeal squamous cell carcinoma and to find out the correlation between the incidence of microsatellite LOH and the clinicopathological parameters Methods Tumor tissues were obtained from paraffin embedded sections with microdissection Genomic DNA was extracted from tumor tissues and peripheral blood lymphocytes with the phenol-chloroform Polymerase chain reaction (PCR) amplification and denaturing gel electrophoresis were carried out in a set of 42 squamous cell carcinoma (SCC) of larynx and corresponding peripheral blood lymphocytes using 13 highly polymorphic microsatellite markers on 9p13-23 The correlation was analyzed between microsatellite LOH at the high frequency on 9p13-23 and clinicopathological parameters in the patients with squamous cell carcinoma of larynx KH*2/5DResults Of the 42 laryngeal cancers, 41 (97 6%) showed LOH in at least one of the microsatellite markers tested on 9p13-23 The most frequently deleted marker was D9S162 in 17 of the 19 (89 5%) informative samples The marker D9S171, which is located on 9p21, had LOH detected in 12 of the 15 informative cases (80 0%) LOH at the D9S1748 marker (closest to the p16 gene locus) was detected in 18 of the 36 informative cases (50 0%) Allelic deletion mapping revealed two minimal regions of LOH encompassing markers D9S161-D9S171 on 9p21 and IFNA-D9S162 on 9p22-23 Multiple LOH (≥4) on 9p21-23 was found more frequently in the patients under 60 years, with supraglottic SCC or cervical lymph node metastasis than those over 60 years, with glottic SCC or without cervical lymph node metastasis ( P <0 01 or 0 01, 0 05, respectively) On the contrary, there was no correlation between T stages or pathologic classification and the frequency of LOH on 9p21-23 in 42 SCC of Larynx Conclusions These findings imply the presence of at least two putative tumor suppressor genes on 9p13-23 in laryngeal SCC Multiple genetic alterations are probably implicated in supraglottic SCC with cervical lymph node metastasis in younger patients展开更多
Esophageal cancer (EC) is one of the most common malignancies in China. Genetic epidemiologic surveys carried out in high-incidence areas of North China have revealed that some genetic factors are involved in pathogen...Esophageal cancer (EC) is one of the most common malignancies in China. Genetic epidemiologic surveys carried out in high-incidence areas of North China have revealed that some genetic factors are involved in pathogenesis of this human cancer. Cytogenetic analyses have shown that nonrandom chromosomal rearrangements, including breakage, translocation and deletion, can be found in esophageal cancer cells as well as in展开更多
Loss of heterozygosity (LOH) is a phenomenon in which elimination of one parental genomic region occurs in interspecific hybrids. LOH is common in cancer (Deng et al., 1996;Koufos et al., 1985). However, genetic analy...Loss of heterozygosity (LOH) is a phenomenon in which elimination of one parental genomic region occurs in interspecific hybrids. LOH is common in cancer (Deng et al., 1996;Koufos et al., 1985). However, genetic analysis of LOH has been mainly conducted based on predetermined features of individual genomes.展开更多
基金Supported by Yunnan Provincial Department of Science and Technology Provincial Basic Research Program(Kunming Medical Joint Special Project,No.2019FE001(-276)Kunming Health Science and Technology Talents Training Project and"Ten Hundred Thousands"Project Training Plan,No.2020-SW(Backup)-121.
文摘BACKGROUND The research findings suggest that the prognosis of children with Wilms tumor(WT)is affected by various factors.Some scholars have indicated that loss of heterozygosity(LOH)on chromosome 16q is associated with a poor prognosis in patients with WT.AIM To further elucidate this relationship,we conducted a meta-analysis.METHODS This meta-analysis was registered in INPLASY(INPLASY2023100060).We systematically searched databases including Embase,PubMed,Web of Science,Cochrane,and Google Scholar up to May 31,2020,for randomized trials reporting any intrapartum fetal surveillance approach.The meta-analysis was performed within a frequentist framework,and the quality and network inconsistency of trials were assessed.Odds ratios and 95%CIs were calculated to report the relationship between event-free survival and 16q LOH in patients with WT.RESULTS Eleven cohort studies were included in this meta-analysis to estimate the relationship between event-free survival and 16q LOH in patients with WT(I^(2)=25%,P<0.001).As expected,16q LOH can serve as an effective predictor of eventfree survival in patients with WT(risk ratio=1.95,95%CI:1.52–2.49,P<0.001).CONCLUSION In pediatric patients with WT,there exists a partial correlation between 16q LOH and an unfavorable treatment prognosis.Clinical detection of 16q chromosome LOH warrants increased attention to the patient’s prognosis.
基金National Natural Science Foundation of China,No.30070043"10.5"Scientific Research Foundation of PLA,No.01Z075
文摘AIM To correlate the length of the telomere to microsatellite instability (MSI) and loss of heterozygosity (LOH) of APC, MCC and DCC genes in gastric carcinomas.METHODS Telomeric restriction fragment (TRF) length of gastric cancer was measured with Southern blot. LOH of APC, MCC and DCC genes, microsatellite instability (MSI) and frameshift mutation of hMSH6, TGF-βR Ⅱ and BAX genes were analyzed by PCR-based methods.RESULTS Sixty-eight cases of sporadic gastric carcinoma were studied for MSI using five microsatellite markers. MSI in at least one locus was detected in 17 (25%) of 68 tumors analyzed. Frameshift mutations of hMSH6, TGF-βR Ⅱ and BAX were detected in 2,6 and 3 of gastric carcinomas respectively showing high MSI (≥ 2 loci, n = 8), but none was found in those showing Iow MSI (only one locus, n = 9) or MSS (tumor lacking MSI or stable, n = 51). Thirty-five cases, including all high MSI and Iow MSl, were studied for TRF. The mean TRF length was not correlated with clinicopathological parameters.No association was observed between TRF length and MSI or frameshift mutation. On the contrary, LOH at the DCC locus was related to telomere shortening (P< 0.01). This tendency was also observed in APC and MCC genes,although there was no statistical significance.CONCLUSION The development of gastric cancer can arise through two different genetic pathways. In high MSI gastric cancers, defective mismatch repair allows mutations to accumulate and generate the high MSI phenotype. In gastric cancers showing either Iow MSI or MSS, multiple deletions may represent the LOH pathway.Telomere erosion is independent of high MSI phenotype but related to the LOH pathway in gastric cancer.
基金supported by the Chinese High-Tech Program(863)Chinese Key Basic Research Project(973)the National Natural Science Foundation of China.Gratitude was extended to Prof.Zhu CHEN for his suggestion and direction of this work.
文摘To elucidate the molecular pathology underlying the development of hepatocellular carcinoma (HCC), we used 41 highly polymorphic microsatellite markers to examine 55 HCC and corresponding non-tumor liver tissues on chromosome 9, 16 and 17. Loss-of-heterozygosity (LOH) is observed with high frequency on chromosomal region 17p13 (36/55, 65%), 9p21-p23 (28/55, 51%), 16q21-q23 (27/55, 49%) in tumors. Meanwhile, microsatellite instability is rarely found in these microsatellite loci. Direct sequencing was performed to detect the tentative mutation of tumor suppressor genes in these regions: p53, MTS1/p16, and CDH1/E-cadherin. Within exon 5-9 of p53 gene, 14 out of 55 HCC specimens (24%) have somatic mutations, and nucleotide deletion of this gene is reported in HCC for the first time. Mutation in MTS1/pl6 is found only in one tumor case. We do not find mutations in CDH1/E-cadherin. Furthermore, a statistically significant correlation is present between p53 gene mutation and loss of chromosome region 16q21q23 and 9p21-p23, which indicates that synergism between p53 inactivation and deletion of 16q21-q23 and 9p21-p23 may play a role in the pathogenesis of HCC. Genetic aberration in hepatocellular
基金This study was supported by grant from the National 973 Project of China (G2000016105)National High Technology Development Project (2002AA211041)the National Natural Science Foundation of China (30500358).
文摘To investigate the correlation of individual heterozygosity and heterosis of three traits in crossbred F1 pig populations, the F1 populations were built by random mating Yorkshire x Meishan (YM, n = 82), and its reciprocal (MY, n =47) and two straightbred populations (Yorkshire = 34, Meishan = 55) were used as control groups. The heterosis of birth weight (BWT), average daily gain (ADG), and feed conversion ratio (FCR) were acquired as well. In the research, the significant marker loci for the heterosis of the three traits were observed by one-way ANOVA (P〈0.01) in a total of 39 marker loci on SSC4, SSC6, SSC7, SSC8, and SSC13, and the numbers of the significant marker loci were 12 (BWT), 18 (ADG), and 17 (FCR), respectively, based on which the general heterozygosity (GH) was divided into significant marker loci heterozygosity (SH) and insignificant marker loci heterozygosity (IH). Furthermore, the trends of alteration in heterosis with the stepwise increase in heterozygosity by 0.05 were explored. This was done by the regression analysis of the three kinds of heterozygosity against heterosis of the three traits. The results showed that, for BWT, the heterosis increased with the increase in GH (r=0.9337, P=0.0021) and SH (r=0.9165, P=0.0102); for ADG, the heterosis increased with the increase in IH (r=0.7012, P=0.0353) and GH (r=0.7470, P=0.0537, near significant); for FCR, the heterosis of feed efficiency increased with the increase in IH (r=0.8721, P=0.0022). The results indicated that the correlation was not always higher or more significant for SH with heterosis than it was for IH or GH with heterosis, and it might be because of the reciprocal cancellation of the positive effect and negative effect of QTL linked to the significant marker loci.
文摘Oligodendroglial tumors frequently have deletions ofchromosomal loci on lp and l9q.Loas of heterozygosity(LOH)of chromosome 10 may be a negative prognostic factor.We reviewed 23 patients with oligodendroglial tumors,toevaluate the frequency of lp and 10q LOH and correlate with clinical outcome.Three loci(DlS402,DlSl 172,MCT118)on lp and 2 loci(Dl0S520 and D10S521)on 10q were analyzed for LOH using PCR techniques.
文摘Objective: To analysis the chromosome 8 heterozygosity loss in human prostate carcinoma and high grade prostatic intraepithelial neoplasia. Methods: Pure DNA was obtained from prostate neoplasms and normal tissues by tissue microdissection. The chromosome 8 heterozygosity loss was detected by PCR based micro-satellite polymorphism analysis technique using 14 pairs of microsatellite primers in 10 samples of prostate carcinoma and 10 samples of high grade prostatic intraepithelial neoplasia. Results: There were different frequencies of chromosome 8 heterozygosity loss in 10 samples of prostate carcinoma. 8p23.1-p23.2 and p21-p22 were two high frequency heterozygosity loss regions. Chromosome 8 heterozygosity loss was detected in 3 samples of high grade prostatic intraepithelial neoplasia. Conclusion: There were high frequency heterozygosity loss regions on chromosome 8 of prostate carcinoma, located at 8p23.1-p23.2 and p21-p22. The high grade prostatic intraepithelial neoplasia and prostate carcinoma share the same allelic loss on 8p. Tumor suppressor genes located at these two regions may be potentially involved in the initiation and progression of prostate carcinoma.
基金This work was supported by the National Natural Science Foundation of China (No.39870753).
文摘Objective: Clinically, the reason of resistance for breast cancer to endocrine therapy has not been well known. The current study attempted to examine loss of heterozygosity (LOH) on the estrogen receptor (ER) gene in breast cancer and its relationship to clinicopathologic findings. Methods: DNAs of tumor tissues and blood lymphocytes were collected from 40 cases of primary breast cancer patients and LOH were detected using the microsatellite repeat assay and combined with other ER immunohistochemical assays. Results: ER-positive staining was observed in 65% of breast cancer. Heterogeneity of ER expression was found. Seven of the patients (17.5%) showed LOH. In three of the seven cases, there was total loss, and there was a marked reduction in the intensity of signal in the other four cases. LOH was associated with histologic grade, occurring more frequently in ER-negative and lymph node metastasis group, but not with tumor size and patient ages. Conclusion: This result implied that LOH of the ER gene may have an important role in the progression of breast cancer. It was postulated that the lack of ER function induced by LOH may contributed to endocrine therapy resistance of breast cancer since the tumor clone would escape from the ER regulation, obtain growth predisposition and finally lost response to therapy.
文摘Southern hybridization was done on DNA samples of22 gastric tumors and corresponding normal tissues, 14colorectal tumors and corresponding normal tissues by probe phs53B mapping at 17P13.1 and probe PYNZ22mapping at 17pl3.3 which were purchased from the American Type Culture Collection. RFLP heterozygosity was observed in 12 normal tissues of gastric cancers and 10 normal tissues of colorectal cancers. Among these informative tumors, 6(50%) cases of gastric cancers and 6(60%) cases of colorectal cancers showed the loss of beterozygosity at 17p13. Our results demonstrated that the inactivation of wild type p53 might be involved in the carcinogenesis of gastric cancers and colorectal cancers.Furthermore, the mode of inactivation of p53 was in accord with the 'two hits' hypothesis by Anudson. The signincance was discussed regarding the presence of LOH detected by probe PYNZ22 mapping at 17pl3.3.
文摘To investigate whether aberration of the APC gene play any role in the development of Chinese sporadic colorectal carcinomas,we used a polymorphic site located in exon 11 which creted a new restriction site for RsaI to analyze LOH for the APC gene.We found that 20/29(68.9%) patients with colorectal cancer were informative for the APC exon 11 site and loss of one allele was detected in 40% of 20 informativc cascs.These data suggested that loss of heterozygosity of APC gene(APC-LOH) play a role in the pathogenesis of Chinese colorectal cancer.APC-LOH is a earlier event of colorectal tumorigenesis and may be of diagnostic value in Patient suffering colorectal cancer.
文摘Objective To analyze the loss of heterozygosity (LOH) for markers on chromosew 22 (CHR 22 ) and its significance with their clinical behaviors. Methods The frequency of CHR22 LOH in 36 schwannomas was observed by denatured polyacrylamide gels and silver staining, and the proliferative index of schwannoma wes calculated by Ki-67 and PCNA immunohistochemistry. Results 15 schwannomas (41. 6% ) shawed allele lass. The proliferative index of schwannomas with LOH were significantly higher than those without LOH (P< 0. 05). In acoustic neuromas, patients with LOH were younger at the age of diagnosis, larger size of tumor, shorter history and higher growth rate than those without LOH, but with no significance. Conclusion CHR22 IDH was the frequent event in the tumorigenesis of sporadic schwannoma. There were some links beteen CHR22 LOH and clinical behavior.
文摘function.FHIT is a potential tumor suppressor gene.Although the precise FHIT molecular mechanism of action is not well understood,evidences suggest that Fhit protein reduced levels are involved in mammary carcinogenesis.The aim of this study was to investigate if FHIT LOH could influence on sporadic breast cancer(BC)biological behavior,through its association with prognostic factors for sporadic BC.Tumor tissue and peripheral blood samples were analyzed using the microsatellite marker D3S1300.The findings were associated with clinicopathological parameters including overall survival.LOH was detected in 31.1%(52/167)of the informative BC’cases.Considering clinical and pathological characteristics we have found no significant association with FHIT LOH status.The mean follow-up time was 80 months.After the Cox regression analysis two parameters remained associated with BC’s risk of death:TNM stage III and IV-HR=3.74(95%CI,1.16-12.1)P=0.027 and disease relapse HR=3.14(CI 95%1.26-7.80)P=0.014.This study shows that FHIT LOH by itself is not a prognostic factor for sporadic BC.Further researches are required to elucidate the functional role of FHIT LOH concerning to BC.
文摘Germ cell tumors complicated by hematological malignancy(HM)are a rare clinical phenomenon.Allogeneic hematopoietic stem cell transplantation(allo-HSCT)is a potentially effective therapy,but graft-versus-host disease(GVHD)is a life-threatening complication.We report a case of a 13-year-old female patient diagnosed with germ cell tumors followed by acute lymphoblastic leukemia.After chemotherapy,she received allo-HSCT and her chimerism rate decreased rapidly to near zero by 6 months without evidence of HM recurrence.However,she developed severe,multiorgan GVHD-like manifestations.DNA analysis revealed the pathogenesis of GVHD to be loss of HLA heterozygosity in recipient hematopoietic cells.
基金supported by the National Natural Science Foundation of China (21621004, 21750001 and 21676192)Young Elite Scientist Sponsorship Program by CAST (YESS) (2018QNRC001)
文摘Genetic variation drives phenotypic evolution within populations. Genetic variation can be divided into different forms according to the size of genomic changes. However, study of large-scale genomic variation such as structural variation and aneuploidy is still limited and mainly based on the static, predetermined feature of individual genomes. Here, using SCRaMbLE,different levels of loss of heterozygosity(LOH) events including short-range LOH, long-range LOH and whole chromosome LOH were detected in evolved strains. By contrast, using rapid adaptive evolution, aneuploidy was detected in the adaptive strains. It was further found that deletion of gene GLN3, long-range LOH in the left arm of synthetic chromosome Ⅹ, whole chromosome LOH of synthetic chromosome Ⅹ, and duplication of chromosome Ⅷ(trisomy) lead to increased rapamycin resistance in synthetic yeast. Comparative analysis of genome stability of evolved strains indicates that the aneuploid strain has a higher frequency of degeneration than the SCRaMbLEd strain. These findings enrich our understanding of genetic mechanism of rapamycin resistance in yeast, and provide valuable insights into yeast genome architecture and function.
文摘Background Schwannoma is the tumor arising mainly from the cranial and spinal nerves. Bilateral vestibular schwannoma is the hallmark of neurofibromatosis type 2 (NF2). The NF2 gene has been cloned with comprehensive analysis of its mutations in schwannoma. However, most studies focused on vestibular schwannoma. There are differences in proliferation of tumor cell and uhrastructure between vestibular and spinal schwannomas. It is unknown whether genetic alterations in vestibular schwannoma are different from those in non-vestibular schwannoma. We analyzed the loss of heterozygosity (LOH) on chromosome 22 in patients with sporadic schwannoma including vestibular and spinal schwannomas and correlated this genetic alteration with tumor proliferation. Methods In 54 unrelated patients without clinical NF1 or NF2, 36 patients had sporadic vestibular schwannoma, and 18 dorsal spinal root schwannoma. Four highly polymorphic linkage to NF2 gene microsatellite DNA markers (D22S264, D22S268, D22S280, CRYB2) were used to analyze LOH. The proliferative index was evaluated by Ki-67 and proliferative cell nuclear antigen (PCNA) immunostaining. Student's t test was used to analyze the difference of the proliferative index between schwannoma with LOH and that without LOH. The difference of the frequency of LOH in vestibular and spinal schwannomas was investigated by the chi-square test. Results Twenty-three schwannomas (42. 6% , 23/54) showed allele loss. The frequency of LOH in vestibular schwannoma was significantly higher than that in spinal schwannoma ( X^2 = 5.14, P 〈 0.05 ). The proliferative index of schwannoma with LOH was significantly higher than that without LOH (tki-67 = 2. 97, P= 0. 0045 ; tPCNA =2.93, P =0. 0051). Conclusions LOH on chromosome 22 is a frequent there is a correlation between LOH on chromosome 22 event in the tumorigenesis of sporadic schwannoma. And, and proliferative activity in schwannoma. The frequency of LOH in vestibular schwannoma is significantly different from that in spinal schwannoma.
基金ThisstudywassupportedbytheNationalNaturalScienceFoundationofChina (No 395 70 714 )
文摘To further illustrate the roles of p53 gene, epidermal growth factor receptor (EGFR) gene and loss of heterozygosity (LOH) on chromosome 10 and 17?p in human glioma progression Methods p53 mutations were scanned in 50 gliomas with various malignant grades using the polymerase chain reaction single strand conformation polymorphism (PCR SSCP) assay, and were confirmed by direct sequencing LOH for chromosome 10, 17?p and amplification of the EGFR gene were also assessed using Southern blot analysis Results p53 mutations were found in 9 of 17 high grade astrocytomas (53%), 1 of 15 low grade astrocytomas (7%), and the only subject of eppendymoblastoma but in none of the 10 medulloblastomas and 7 eppendymomas The majority of gliomas (38/50) analyzed here retained both 17?p alleles The frequency of p53 mutations was 13% in this group of tumors and increased to 50% (6/12) in tumors with one 17?p allele ( P <0 025) LOH on chromosome 10 was found in 35% (6/17) of high grade astrocytomas, in 10% (1/10) of medulloblastomas, but in 0% of low grade gliomas EGFR gene amplification was found in 9 high grade gliomas, 60% (6/9) of which also presented LOH for chromosome 10 Conclusions These results indicate that p53 inactivation is a common genetic event in astrocytoma progression that may be more strongly associated with the progression of astrocytomas than with their origin Absence of p53 mutations in 50% of the tumors with one 17?p allele suggests that a tumor suppressor gene other than p53 may be located on chromosome 17?p and involved in progression to malignancy of some gliomas The loss of alleles on chromosome 10 and the amplification of the EGFR gene appear to be restricted to high grade tumors, suggesting that these events may be related to tumor progression rather than initiation
文摘Background This study was designed to investigate the hot spots of microsatellite loss of heterozygosity (LOH) on 9p13-23 in laryngeal squamous cell carcinoma and to find out the correlation between the incidence of microsatellite LOH and the clinicopathological parameters Methods Tumor tissues were obtained from paraffin embedded sections with microdissection Genomic DNA was extracted from tumor tissues and peripheral blood lymphocytes with the phenol-chloroform Polymerase chain reaction (PCR) amplification and denaturing gel electrophoresis were carried out in a set of 42 squamous cell carcinoma (SCC) of larynx and corresponding peripheral blood lymphocytes using 13 highly polymorphic microsatellite markers on 9p13-23 The correlation was analyzed between microsatellite LOH at the high frequency on 9p13-23 and clinicopathological parameters in the patients with squamous cell carcinoma of larynx KH*2/5DResults Of the 42 laryngeal cancers, 41 (97 6%) showed LOH in at least one of the microsatellite markers tested on 9p13-23 The most frequently deleted marker was D9S162 in 17 of the 19 (89 5%) informative samples The marker D9S171, which is located on 9p21, had LOH detected in 12 of the 15 informative cases (80 0%) LOH at the D9S1748 marker (closest to the p16 gene locus) was detected in 18 of the 36 informative cases (50 0%) Allelic deletion mapping revealed two minimal regions of LOH encompassing markers D9S161-D9S171 on 9p21 and IFNA-D9S162 on 9p22-23 Multiple LOH (≥4) on 9p21-23 was found more frequently in the patients under 60 years, with supraglottic SCC or cervical lymph node metastasis than those over 60 years, with glottic SCC or without cervical lymph node metastasis ( P <0 01 or 0 01, 0 05, respectively) On the contrary, there was no correlation between T stages or pathologic classification and the frequency of LOH on 9p21-23 in 42 SCC of Larynx Conclusions These findings imply the presence of at least two putative tumor suppressor genes on 9p13-23 in laryngeal SCC Multiple genetic alterations are probably implicated in supraglottic SCC with cervical lymph node metastasis in younger patients
文摘Esophageal cancer (EC) is one of the most common malignancies in China. Genetic epidemiologic surveys carried out in high-incidence areas of North China have revealed that some genetic factors are involved in pathogenesis of this human cancer. Cytogenetic analyses have shown that nonrandom chromosomal rearrangements, including breakage, translocation and deletion, can be found in esophageal cancer cells as well as in
文摘Loss of heterozygosity (LOH) is a phenomenon in which elimination of one parental genomic region occurs in interspecific hybrids. LOH is common in cancer (Deng et al., 1996;Koufos et al., 1985). However, genetic analysis of LOH has been mainly conducted based on predetermined features of individual genomes.