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
制备α1,3-半乳糖基转移酶(αl,3-galactosyltransferase,GGTA1)基因缺失的五指山小型猪,为我国异种器官移植研究奠定基础。在已经获得的GGTA1单等位基因敲除(GGTA+/-)五指山小型猪基础上,建立GGTA1+/-猪耳成纤维细胞系。利用特异性结合...制备α1,3-半乳糖基转移酶(αl,3-galactosyltransferase,GGTA1)基因缺失的五指山小型猪,为我国异种器官移植研究奠定基础。在已经获得的GGTA1单等位基因敲除(GGTA+/-)五指山小型猪基础上,建立GGTA1+/-猪耳成纤维细胞系。利用特异性结合α1,3Gal的药物GSI-B4联合免疫磁珠筛选,成功分离出自发杂合性缺失(Loss of heterozygosity,LOH)的双等位基因敲除(GGTA1-/-)耳成纤维细胞。单细胞克隆培养与PCR鉴定后,以GGTA1-/-细胞为核供体,体外成熟的猪卵母细胞为核受体构建克隆胚胎并移植。先后将3 122枚重构胚移植到13头受体母猪,其中4头怀孕,产仔12头。采用PCR和Southern blotting进行GGTA1基因型检测,11头为GGTA1-/-猪;流式细胞术分析表明,GGTA1-/-仔猪耳成纤维细胞不表达α1,3Gal。获得能克服异种器官超急性排斥反应(HAR)的GGTA1-/-猪,不仅为异种器官供体的进一步基因修饰提供了平台,也为异种移植临床前研究提供了宝贵资源。展开更多
中国龙船花Ixora chinensis是一种兼备药用与观赏价值的传统中药材,解析中国龙船花的基因组特征信息,可为其全基因组测序和药效成分生物合成的分子机制研究奠定理论基础。本研究利用Survey基因组测序技术,使用K-mer分析方法对中国龙船...中国龙船花Ixora chinensis是一种兼备药用与观赏价值的传统中药材,解析中国龙船花的基因组特征信息,可为其全基因组测序和药效成分生物合成的分子机制研究奠定理论基础。本研究利用Survey基因组测序技术,使用K-mer分析方法对中国龙船花基因组特征信息展开评估,获得基因组重复度、杂合度以及GC含量等信息。Survey高通量测序获得Raw Data 47.63 Gb,过滤后Clean data 45.62 Gb。K-mer分析表明,基因组大小588.35 Mb,杂合度1.5598%,重复度64.49%,GC含量35.71%,中国龙船花基因组呈现高杂合度、高重复度、基因组庞大的特征。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
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
AIM: To investigate the loss of heterozygosity (LOH) and mutation of tumor suppressor gene PTEN in gastric cancer and precancerous lesions.METHODS: Thirty cases of normal gastric mucosa, advanced and early stage gastr...AIM: To investigate the loss of heterozygosity (LOH) and mutation of tumor suppressor gene PTEN in gastric cancer and precancerous lesions.METHODS: Thirty cases of normal gastric mucosa, advanced and early stage gastric cancer, intestinal metaplasia, atrophic gastritis, and atypical hyperplasia were analyzed for PTEN LOH and mutations within the entire coding region of PTEN gene by PCR-SSCP denaturing PAGE gel electrophoresis,and PTEN mutation was detected by PCR-SSCP sequencing followed by silver staining.RESULTS: LOH rate found in respectively atrophic gastritis was 10% (3/30), intestinal metaplasia 10% (3/30), atypical hyperpiasia 13.3% (4/30), early stage gastric cancer 20%(6/30), and advanced stage gastric cancer 33.3% (9/30),None of the precancerous lesions and early stage gastric cancer showed PTEN mutations, but 10% (3/30) of the advanced stage gastric cancers, which were all positive for LOH, showed PTEN mutation.CONCLUSION: LOH of PTEN gene appears in precancerous lesions, and PTEN mutations are restricted to advanced gastric cancer, LOH and mutation of PTEN gene are closely related to the infiltration and metastasis of gastric cancer.展开更多
AIM:To investigate genes around the locus D4S2964 affected by loss of heterozygosity(LOH) and their clinical implications.METHODS:Four hundred and forty single nucleotide polymorphisms(SNPs) located at 49 genes around...AIM:To investigate genes around the locus D4S2964 affected by loss of heterozygosity(LOH) and their clinical implications.METHODS:Four hundred and forty single nucleotide polymorphisms(SNPs) located at 49 genes around D4S2964 were selected from the National Center for Biotechnology Information website for the SNPs microarray fabrication.LOH of SNPs markers in 112 cases of hepatocellular carcinoma(HCC) tissues and paired adjacent liver tissues were investigated by the SNPs microarray.The correlation between allelic losses with clinicopathological features and overall survival was analyzed.RESULTS:A f ine map of LOH of SNPs in genes around D4S2964 was plotted.The average frequency of LOH in genes was 0.39.A correlation between cirrhosis and the FAL index(fractional allelic loss) was found(P = 0.0202).Larger tumor size was found to be signif icantly associated with LOH in genes ADP-ribosyltransferase 3(ART3),nucleoporin 54 kDa(NUP54),scavenger receptor class B,member 2(SCARB2) and coiled-coil domain containing 158(CCDC158)(P = 0.043,P = 0.019,P = 0.001,P = 0.037,respectively).Kaplan-Meier analysis showed that patients with LOH in ARD1 homolog B(ARD1B) and septin 11(SEPT11) had a significantly lower survival rate than those with retention(P = 0.021 and P = 0.004,respectively).A Cox regression model suggested that LOH in ARD1B and SEPT11,respectively,were predictors of the overall survival in HCC(P = 0.006 and P = 0.026,respectively).CONCLUSION:LOH in genes around D4S2964 may play an important role in HCC development and progression.LOH in ARD1B and SEPT11 could serve as novel prognostic predictors in HCC patients.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.
文摘制备α1,3-半乳糖基转移酶(αl,3-galactosyltransferase,GGTA1)基因缺失的五指山小型猪,为我国异种器官移植研究奠定基础。在已经获得的GGTA1单等位基因敲除(GGTA+/-)五指山小型猪基础上,建立GGTA1+/-猪耳成纤维细胞系。利用特异性结合α1,3Gal的药物GSI-B4联合免疫磁珠筛选,成功分离出自发杂合性缺失(Loss of heterozygosity,LOH)的双等位基因敲除(GGTA1-/-)耳成纤维细胞。单细胞克隆培养与PCR鉴定后,以GGTA1-/-细胞为核供体,体外成熟的猪卵母细胞为核受体构建克隆胚胎并移植。先后将3 122枚重构胚移植到13头受体母猪,其中4头怀孕,产仔12头。采用PCR和Southern blotting进行GGTA1基因型检测,11头为GGTA1-/-猪;流式细胞术分析表明,GGTA1-/-仔猪耳成纤维细胞不表达α1,3Gal。获得能克服异种器官超急性排斥反应(HAR)的GGTA1-/-猪,不仅为异种器官供体的进一步基因修饰提供了平台,也为异种移植临床前研究提供了宝贵资源。
文摘中国龙船花Ixora chinensis是一种兼备药用与观赏价值的传统中药材,解析中国龙船花的基因组特征信息,可为其全基因组测序和药效成分生物合成的分子机制研究奠定理论基础。本研究利用Survey基因组测序技术,使用K-mer分析方法对中国龙船花基因组特征信息展开评估,获得基因组重复度、杂合度以及GC含量等信息。Survey高通量测序获得Raw Data 47.63 Gb,过滤后Clean data 45.62 Gb。K-mer分析表明,基因组大小588.35 Mb,杂合度1.5598%,重复度64.49%,GC含量35.71%,中国龙船花基因组呈现高杂合度、高重复度、基因组庞大的特征。
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 National Natural Science Foundation of China,No. 30070845
文摘AIM: To investigate the loss of heterozygosity (LOH) and mutation of tumor suppressor gene PTEN in gastric cancer and precancerous lesions.METHODS: Thirty cases of normal gastric mucosa, advanced and early stage gastric cancer, intestinal metaplasia, atrophic gastritis, and atypical hyperplasia were analyzed for PTEN LOH and mutations within the entire coding region of PTEN gene by PCR-SSCP denaturing PAGE gel electrophoresis,and PTEN mutation was detected by PCR-SSCP sequencing followed by silver staining.RESULTS: LOH rate found in respectively atrophic gastritis was 10% (3/30), intestinal metaplasia 10% (3/30), atypical hyperpiasia 13.3% (4/30), early stage gastric cancer 20%(6/30), and advanced stage gastric cancer 33.3% (9/30),None of the precancerous lesions and early stage gastric cancer showed PTEN mutations, but 10% (3/30) of the advanced stage gastric cancers, which were all positive for LOH, showed PTEN mutation.CONCLUSION: LOH of PTEN gene appears in precancerous lesions, and PTEN mutations are restricted to advanced gastric cancer, LOH and mutation of PTEN gene are closely related to the infiltration and metastasis of gastric cancer.
基金Supported by National Natural Science Foundation of China,No. 30772491 to Wang HYpartially supported by Research Fund of State Key Laboratory of Oncology in South China to Wang HY
文摘AIM:To investigate genes around the locus D4S2964 affected by loss of heterozygosity(LOH) and their clinical implications.METHODS:Four hundred and forty single nucleotide polymorphisms(SNPs) located at 49 genes around D4S2964 were selected from the National Center for Biotechnology Information website for the SNPs microarray fabrication.LOH of SNPs markers in 112 cases of hepatocellular carcinoma(HCC) tissues and paired adjacent liver tissues were investigated by the SNPs microarray.The correlation between allelic losses with clinicopathological features and overall survival was analyzed.RESULTS:A f ine map of LOH of SNPs in genes around D4S2964 was plotted.The average frequency of LOH in genes was 0.39.A correlation between cirrhosis and the FAL index(fractional allelic loss) was found(P = 0.0202).Larger tumor size was found to be signif icantly associated with LOH in genes ADP-ribosyltransferase 3(ART3),nucleoporin 54 kDa(NUP54),scavenger receptor class B,member 2(SCARB2) and coiled-coil domain containing 158(CCDC158)(P = 0.043,P = 0.019,P = 0.001,P = 0.037,respectively).Kaplan-Meier analysis showed that patients with LOH in ARD1 homolog B(ARD1B) and septin 11(SEPT11) had a significantly lower survival rate than those with retention(P = 0.021 and P = 0.004,respectively).A Cox regression model suggested that LOH in ARD1B and SEPT11,respectively,were predictors of the overall survival in HCC(P = 0.006 and P = 0.026,respectively).CONCLUSION:LOH in genes around D4S2964 may play an important role in HCC development and progression.LOH in ARD1B and SEPT11 could serve as novel prognostic predictors in HCC patients.
