CHROMOSOME 17P MAY HARBOR MULTIPLE TUMOR SUPPRESSOR GENES ASSOCIATED WITH PRIMARY GLIOBLASTOMA MULTIFORME

Objective: To investigate whether deletion of chromosome 17 is involved in the carcinogenesis of primary glioblastoma multiforme and to localize the possible common deletion region in the aforementioned chromosome. Methods: Polymerase chain reaction-based microsatellite analysis was used to assess loss of heterozygosity (LOH) on chromosome 17 in 20 primary glioblastoma multiforme (GBM). Fifteen fluorescent dye-labeled polymorphic markers were used. Results: Thirteen of twenty (65%) GBM displayed LOH on at least one marker of chromosome 17p. Two tumors showed either LOH or non-informativeness on all markers tested. The most frequent LOH was observed at loci including D17s799 (53.3%), D17s1852 (53.8%), D17s938 (63.20/o), D17s831 (55.6%). The loci D17s831 (on 17p13) and D17s799–D17s1852 (17p11.2–p12) are distal and proximal to p53 respectively. The frequencies of LOH at all loci examined on chromosome 17q were relatively low (<30%). None of informative loci exhibited microsatellite instability in this study. Conclusion: Loss of genetic material on chromosome 17p may play an important role in the pathogenesis of GBM. Besides the well-known TSG p53 on 17p, other unknown TSCs associated with GBM may be present on the chromosomal regions 17p13 and 17p11.2–p12, which are distal and proximal to p53 respectively.

Bioinformatics Analysis Revealed Potential Tumor Suppressors (KLF4/CGN), Oncogenes (SHH/LIF) and Biomarkers of Asian Stomach Adenocarcinoma

Stomach adenocarcinoma (STAD) is the fifth most prevalent cancer and the third leading cause of cancer-related death in the world and is more common in Asia than in most Western countries. There is an urgent need to identify potential novel oncogenes and tumor suppressor genes, and biomarkers for STAD. 6652 differentially expressed genes were identified between STAD and normal samples based on the transcriptome data analysis of the TCGA and GEO databases. 13 key modules were identified in STAD by WGCNA analysis. 293 potential STAD associated genes were identified from intersection by Venn Diagram. The 293 intersected genes were enriched in cell cortex and infection by GO and KEGG analysis. 10 hub genes were identified from PPI and Cytoscape analyses of the intersected genes. KLF4/CGN low and SHH/LIF high expression were associated with short overall survival of Asian STAD patients. Bioinformatics analysis revealed potential novel tumor suppressors (KLF4/CGN), oncogenes (SHH/LIF) and biomarkers for diagnosis, therapy and prognosis of STAD, specifically for Asian patients.

Mapping of metastasis suppressor genes for prostate cancer by microcell-mediated chromosome transfer

Aim: To identify the metastasis suppressor genes for prostate cancer. Methods: A copy of human chromosomeswas introduced into the highly metastatic Dunning R-3327 rat prostate cancer cells by the use of microcell-mediatedchromosome transfer. Relationships between the size of human chromosomes introduced into microcell hybrid clonesand the number of lung metastases produced by the clones were analyzed to determine which part of human chromo-somes contained the metastasis suppressor gene (s) for prostate cancer. To determine portions of human chromosomesintroduced, G-banding chromosomal analysis, fluorescence in sim hybridization analysis, and polymerase chain reac-tion analysis were performed. Results: Each of microcell hybrid clones containing human chromosomes 7, 8, 10,11, 12, or 17 showed decreased ability to metastasize to the lung without any loss of tumorigenicity. This demonstratesthat these human chromosomes contain metastasis suppressor genes for prostate cancer. Spontaneous deletion of portionsof human chromosomes was observed in the human chromosome 7, 10, 11, 12, and 17 studies. In the human chromo-some 8 study, irradiated microcell-mediated chromosome transfer was performed to enrich chromosomal arm deletionsof human chromosome 8. Molecular and cytogenetic analyses of microcell hybrid clones demonstrated that metastasissuppressor genes on human chromosomes were located on 7q21-22, 7q31.2-32, 8p21-12, 10q11-22, 11p13-11.2,12p11-q13, 12q24-ter, and 17pter-q23. KAII and MKK4/SEKI were identified as metastasis suppressor genes from11p11. 2 and 17p12, respectively. Conclusion: This assay system is useful to identify metastasis suppressor gene(s) for prostate cancer.

Identification of reference genes provides functional insights into meiotic recombination suppressors in Gerbera hybrida

Gerbera Hybrida is one of the important cut flowers across the world.The novel traits are the primarily market requirements and the breeding targets,mainly determined by the degree of genetic variation after hybridization.However,meiotic recombination is highly conserved in most eukaryotes which suppressed the crossover formation and limited the genetic diversity.Recently,several meiotic recombination suppressors have been identified and characterized in plants,whereas it remains elusive in G.hybrida.In order to characterize the expression patterns of these suppressors in G.hybrida,20 candidate reference genes were identified from the transcriptome datasets of G.hybrida,and their expression stabilities during plant development were evaluated by geNorm,NormFinder and BestKeeper.Although the most stable reference genes were variable in different softwares,comprehensive ranking revealed that PGK2 was the most stable reference gene and GAPDH was the most unstable one.The expression patterns of FANCM,FIGL1,RECQ4,RM1,and FLIP further validated that PGK2 was suitable for normalization of gene expression.Our study identified a reliable reference gene for gene expression during meiotic recombination,and provided functional insights into meiotic recombination suppressors in G.hybrida.

Hepatocellular carcinoma mouse models:Hepatitis B virusassociatedhepatocarcinogenesis and haploinsufficienttumor suppressor genes

The multifactorial and multistage pathogenesis of hepatocellular carcinoma(HCC)has fascinated a wide spectrum of scientists for decades.While a number of major risk factors have been identified,their mechanistic roles in hepatocarcinogenesis still need to be elucidated.Many tumor suppressor genes(TSGs)have been identified as being involved in HCC.These TSGs can be classified into two groups depending on the situation with respect to allelic mutation/loss in the tumors:the recessive TSGs with two required mutated alleles and the haploinsufficient TSGs with one required mutated allele.Hepatitis B virus(HBV)is one of the most important risk factors associated with HCC.Although mice cannot be infected with HBV due to the narrow host range of HBV and the lack of a proper receptor,one advantage of mouse models for HBV/HCC research is the numerous and powerfulgenetic tools that help investigate the phenotypic effects of viral proteins and allow the dissection of the dose-dependent action of TSGs.Here,we mainly focus on the application of mouse models in relation to HBV-associated HCC and on TSGs that act either in a recessive or in a haploinsufficient manner.Discoveries obtained using mouse models will have a great impact on HCC translational medicine.

CHROMOSOME 3 MAY HARBOR MULTIPLE TUMOR SUPPRESSOR GENES ASSOCIATED WITH PRIMARY GLIOBLASTOMA MULTIFORME

Objective: To investigate whether deletion of chromosome 3 is involved in the carcinogenesis of primary glioblastoma multiforme (GBM) and to localize the possible common deletion region in the aforementioned chromosome. Methods: PCR based microsatellite polymorphism analyses were performed to detect loss of heterozygosity (LOH). Twenty-three loci on chromosome 3 were examined in 20 cases of GBM. Fluorescence-labeled primers and Perkin Elmer 377 DNA Sequencer were applied. Results: 50% informative cases of GBM displayed LOH on chromosome 3. 50% of informative cases displayed LOH on 3q and 35% on 3p. 25.6% of informative loci showed LOH in our series, in which frequent LOH were observed in the chromosomal region from loci D3S1614 (42.9%) to D3S1565 (35.3%) on 3q24–27 and at loci D3S1569 (35.3%) on 3q22–23 and D3S1289 (33.3%) on 3p14.1–14.3. Conclusion: Loss of genetic material on chromosome 3 may play an important part in the tumorigenesis of GBM. The chromosomal regions from loci D3S1614 to D3S1565 on 3q24–27 and at loci D3S1569 on 3q22–23 and D3S1289 on 3p14.1–14.3 are potential sites for novel tumor suppressor genes associated with GBM.

Correlation research of Runt-related transcription factor 2 with proliferation genes, tumor suppressor genes and angiogenesis molecules in colon cancer lesions

Objective: To investigate the correlation of Runt-related transcription factor 2 (RunX2) with proliferation genes, tumor suppressor genes and angiogenesis molecules in colon cancer lesions. Methods: A total of 90 patients with primary colon cancer were enrolled in colon cancer group, 68 patients with benign colon polyps were enrolled in colon polyps group, the differences in the expression levels of RunX2, proliferation genes, tumor suppressor genes and angiogenesis molecules in the two groups of lesions were compared, and Pearson test was further used to evaluate the correlation of RunX2 expression level with proliferation gene, tumor suppressor gene and angiogenesis molecule expression levels in colon cancer tissues. Results: RunX2 mRNA expression level in the lesions of colon cancer group was higher than that of colon polyps group. Proliferation genes GTPBP4, HOXB7, ZNF331, ADAM17 and HSP60 mRNA expression levels in the lesions of colon cancer group were higher than those of colon polyps group;tumor suppressor genes ATF3, FOXN3, OTUD1 and NDRG2 mRNA expression levels were lower than those of colon polyps group;angiogenesis molecules Musashi 1, NF-κB, RegⅣ and STAT3 mRNA expression levels were higher than those of colon polyps group. RunX2 mRNA expression level in the colon cancer lesions was directly correlated with the expression levels of the above proliferation genes, tumor suppressor genes and angiogenesis molecules. Conclusion: RunX2 expression is abnormally high in colon cancer lesions, the specific expression level is positively correlated with cancer cell proliferation activity and angiogenesis activity, and it is an important molecular target that can lead to the occurrence and development of colon cancer.

Comprehensive analysis of the potential pathogenesis of COVID-19 infection and liver cancer

BACKGROUND A growing number of clinical examples suggest that coronavirus disease 2019(COVID-19)appears to have an impact on the treatment of patients with liver cancer compared to the normal population,and the prevalence of COVID-19 is significantly higher in patients with liver cancer.However,this mechanism of action has not been clarified.Gene sets for COVID-19(GSE180226)and liver cancer(GSE87630)were obtained from the Gene Expression Omnibus database.After identifying the common differentially expressed genes(DEGs)of COVID-19 and liver cancer,functional enrichment analysis,protein-protein interaction network construction and scree-ning and analysis of hub genes were performed.Subsequently,the validation of the differential expression of hub genes in the disease was performed and the regulatory network of transcription factors and hub genes was constructed.RESULTS Of 518 common DEGs were obtained by screening for functional analysis.Fifteen hub genes including aurora kinase B,cyclin B2,cell division cycle 20,cell division cycle associated 8,nucleolar and spindle associated protein 1,etc.,were further identified from DEGs using the“cytoHubba”plugin.Functional enrichment analysis of hub genes showed that these hub genes are associated with P53 signalling pathway regulation,cell cycle and other functions,and they may serve as potential molecular markers for COVID-19 and liver cancer.Finally,we selected 10 of the hub genes for in vitro expression validation in liver cancer cells.CONCLUSION Our study reveals a common pathogenesis of liver cancer and COVID-19.These common pathways and key genes may provide new ideas for further mechanistic studies.

Relationship of ultrasonic shear wave velocity with oncogene and tumor suppressor gene expression in primary liver cancer lesions as well as angiogenesis factor contents

Objective:To discuss the relationship of ultrasonic shear wave velocity (SWV) with oncogene and tumor suppressor gene expression in primary liver cancer lesions as well as angiogenesis factor contents.Methods:100 patients with primary liver cancer who underwent surgical treatment in our hospital between March 2014 and September 2016 were collected as observation group, and 50 healthy subjects who received physical examination in our hospital during the same period were collected as normal control group. The ultrasonic SWV levels of two groups of subjects were measured before the operation, and the observation groups were further divided into high SWV group and low SWV group, 50 cases in each group. Intraoperative tumor tissue samples were kept and fluorescence quantitative PCR was used to determine the mRNA expression of oncogenes and tumor suppressor genes. Enzyme-linked immunosorbent assay was used to determine serum contents of angiogenesis factors in observation group before operation.Results:Hepatic ultrasonic SWV level in observation group was significantly higher than that in normal control group;proto-oncogene CK, Ki67, Gly-3, Survivin and Pokemon mRNA expression in tumor tissue of high SWV group were higher than those of low SWV group while tumor suppressor genes Tg737, p16, p27, PTEN and runx3 mRNA expression were lower than those of low SWV group;serum angiogenesis factors VEGF, MMP-9 and IGF-1R contents were higher than those in low SWV group. Conclusion: The hepatic ultrasonic SWV level increases in patients with primary liver cancer, and the SWV level is directly correlated with oncogene and tumor suppressor gene expression as well as angiogenesis factor contents.

Potential roles of tumor suppressor genes and microsatellite instability in hepatocellular carcinogenesis in southern African blacks

MAJOR POINTS OF THE COMMENTED ARTICLECumulative loss of heterozygosity(LOH)ofchromosomal regions and tumor suppressor geneshas been reported in hepatocellular carcinomas(HCCs) from China,Japan,and Korea.In thisissue of the World Journal of Gastroenterology,Martins et al report an analysis of LOH andmicrosatellite instability in HCCs from a group of

Hypermethylation of tumor suppressor and tumor-related genes in neoplastic and non-neoplastic gastric epithelia

A number of tumor suppressor and tumor-related genes exhibit promoter hypermethylation with resultant gene silencing in human cancers.The frequencies of methylation differ among genes and genomic regions within CpG islands in different tissue types.Hypermethylation initially occurs at the edge of CpG islands and spreads to the transcription start site before ultimately shutting down gene expression.When the degree of methylation was quantitatively evaluated in neoplastic and non-neoplastic gastric epithelia using DNA microarray analysis,highlevel methylation around the transcription start site appeared to be a tumor-specific phenomenon,although multiple tumor suppressor genes became increasingly methylated with patient age in non-neoplastic gastric epithelia.Quantitative analysis of DNA methylation is a promising method for both cancer diagnosis and risk assessment.

Tumor suppressor genes on frequently deleted chromosome 3p in nasopharyngeal carcinoma

Nasopharyngeal carcinoma (NPC) is among the most common malignancies in southern China.Deletion of genomic DNA,which occurs during the complex pathogenesis process for NPC,represents a pivotal mechanism in the inactivation of tumor suppressor genes (TSGs).In many circumstances,loss of TSGs can be detected as diagnostic and prognostic markers in cancer.The short arm of chromosome 3 (3p) is a frequently deleted chromosomal region in NPC,with 3p21.1-21.2 and 3p25.2-26.1 being the most frequently deleted minimal regions.In recent years,our research group and others have focused on the identification and characterization of novel target TSGs at 3p,such as RASSF1A,BLU,RBMS3,and CHL1,in the development and progression of NPC.In this review,we summarize recent findings of TSGs at 3p and discuss some of these genes in detail.A better understanding of TSGs at 3p will significantly improve our understanding of NPC pathogenesis,diagnosis,and treatment.

Recent progress in the study of methylated tumor suppressor genes in gastric cancer

Gastric cancer is one of the most common malignancies and a leading cause of cancer mortality worldwide.The pathogenesis mechanisms of gastric cancer are still not fully clear.Inactivation of tumor suppressor genes and activation of oncogenes caused by genetic and epigenetic alterations are known to play significant roles in carcinogenesis.Accumulating evidence has shown that epigenetic silencing of the tumor suppressor genes,particularly caused by hypermethylation of CpG islands in promoters,is critical to carcinogenesis and metastasis.Here,we review the recent progress in the study of methylations of tumor suppressor genes involved in the pathogenesis of gastric cancer.We also briefly describe the mechanisms that induce tumor suppressor gene methylation and the status of translating these molecular mechanisms into clinical applications.

Promoter methylation of tumor suppressor genes in esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma(ESCC) is a prevalent and fatal cancer in China and other Asian countries.Epigenetic silencing of key tumor suppressor genes(TSGs) is critical to ESCC initiation and progression.Recently,many novel TSGs silenced by promoter methylation have been identified in ESCC,and these genes further serve as potential tumor markers for high-risk group stratification,early detection,and prognosis prediction.This review summarizes recent discoveries on aberrant promoter methylation of TSGs in ESCC,providing better understanding of the role of disrupted epigenetic regulation in tumorigenesis and insight into diagnostic and prognostic biomarkers for this malignancy.

IKKβ overexpression together with a lack of tumour suppressor genes causes ameloblastic odontomas in mice

Odontogenic tumours are a heterogeneous group of lesions that develop in the oral cavity region and are characterized by the formation of tumoural structures that differentiate as teeth. Due to the diversity of their histopathological characteristics and clinical behaviour, the classification of these tumours is still under debate. Alterations in morphogenesis pathways such as the Hedgehog,MAPK and WNT/β-catenin pathways are implicated in the formation of odontogenic lesions, but the molecular bases of many of these lesions are still unknown. In this study, we used genetically modified mice to study the role of IKKβ(a fundamental regulator of NF-κB activity and many other proteins) in oral epithelial cells and odontogenic tissues. Transgenic mice overexpressing IKKβ in oral epithelial cells show a significant increase in immune cells in both the oral epithelia and oral submucosa. They also show changes in the expression of several proteins and mi RNAs that are important for cancer development. Interestingly, we found that overactivity of IKKβ in oral epithelia and odontogenic tissues, in conjunction with the loss of tumour suppressor proteins(p53, or p16 and p19), leads to the appearance of odontogenic tumours that can be classified as ameloblastic odontomas, sometimes accompanied by foci of secondary ameloblastic carcinomas. These tumours show NF-κB activation and increased β-catenin activity.These findings may help to elucidate the molecular determinants of odontogenic tumourigenesis and the role of IKKβ in the homoeostasis and tumoural transformation of oral and odontogenic epithelia.

The role of XPC protein deficiency in tobacco smoke-induced DNA hypermethylation of tumor suppressor genes

DNA hypermethylation of tumor suppressor genes has been frequently observed in cancer patients, and therefore, may provide a valuable biomarker for cancer prevention and treatment. DNA hypermethylation may also provide an important mechanism in cancer progression. Lung cancer is strongly associated with exposure to environmental carcinogens, especially tobacco smoke. DNA damage generated by tobacco smoke is believed to play an important role in lung cancer development. XPC is a DNA damage recognition protein required for DNA repair and other DNA damage responses and attenuated XPC protein levels have been detected in many lung cancer patients. We studied the role of XPC protein deficiency in tobacco smoke-caused DNA hypermethylation of important tumor suppressor genes. Using both normal human fibroblasts (NF) and XPC-deficient hu man fibroblasts (XPC), our DNA methylation studies demonstrated that the XPC deficiency caused elevated levels of DNA hypermethylation in both Brca1 and Mlh1 tumor suppressor genes following exposure to tobacco smoke condensate (TSC). The results of our ChIP studies revealed that the XPC deficiency led to an increased binding of DNA methyltransferase 3A (DNMT3A) at the promoter region CpG island-containing sequences of these genes under the TSC treatment;however, this increase was partially diminished with prior treatment with caffeine. The results of our immuno-precipitation (IP) studies demonstrated a protein-protein interaction of the ATR with DNMT3A. Our western blots revealed that the XPC deficiency caused an increase in TSC-induced ATR phosphorylation at serine 428, an indicator of ATR activation. All these results suggest that XPC deficiency causes an accelerated DNA hypermethylation in important tumor suppressor genes under tobacco smoke exposure and activation of the ATR signaling pathway is involved in this DNA hypermethylation process.

Science Letters:IGFBP7 plays a potential tumor suppressor role against colorectal carcinogenesis with its expression associated with DNA hypomethylation of exon 1

Insulin-like growth factor binding-protein-7 (IGFBP7) was obtained from our previous colonic adenocarcinoma (CRC) and normal mucosa suppression subtraction hybridization (SSH) cDNA libraries. By RT-PCR and immunohistochemistry, we found that IGFBP7 was overexpressed in CRC tissue compared to normal tissue. However, our in vitro experiments performed in 10 CRC cell lines showed that IGFBP7 expressed only in SW480 and Caco2 cell lines, which implied an underlying reversible regulatory mechanism. Using methylation-specific PCR (MSP) and bisulfite sodium PCR (BSP), we found that its expression was associated with DNA hypomethylation of exon1. This was further supported by the in vitro study which showed restored IGFBP7 expression after demethylation agent 5-aza-2’-deoxycytidine treatment. Correlation analysis between IGFBP7 expression and prognosis indicated that overexpression of IGFBP7 in CRC tissue correlated with favourable survival. Investigation of the func-tional role of IGFBP7 through transfection studies showed that IGFBP7 protein could inhibit growth rate, decrease colony for-mation activity, and induce apoptosis in RKO and SW620 cells, suggesting it a potential tumor suppressor protein in colorectal carcinogenesis. In conclusion, our study clearly demonstrated that IGFBP7 plays a potential tumor suppressor role against colo-rectal carcinogenesis and its expression is associated with DNA hypomethylation of exon 1.

Identification of hub genes associated with Helicobacter pylori infection and type 2 diabetes mellitus:A pilot bioinformatics study

BACKGROUND Helicobacter pylori(H.pylori)infection is related to various extragastric diseases including type 2 diabetes mellitus(T2DM).However,the possible mechanisms connecting H.pylori infection and T2DM remain unknown.AIM To explore potential molecular connections between H.pylori infection and T2DM.METHODS We extracted gene expression arrays from three online datasets(GSE60427,GSE27411 and GSE115601).Differentially expressed genes(DEGs)commonly present in patients with H.pylori infection and T2DM were identified.Hub genes were validated using human gastric biopsy samples.Correlations between hub genes and immune cell infiltration,miRNAs,and transcription factors(TFs)were further analyzed.RESULTS A total of 67 DEGs were commonly presented in patients with H.pylori infection and T2DM.Five significantly upregulated hub genes,including TLR4,ITGAM,C5AR1,FCER1G,and FCGR2A,were finally identified,all of which are closely related to immune cell infiltration.The gene-miRNA analysis detected 13 miRNAs with at least two gene cross-links.TF-gene interaction networks showed that TLR4 was coregulated by 26 TFs,the largest number of TFs among the 5 hub genes.CONCLUSION We identified five hub genes that may have molecular connections between H.pylori infection and T2DM.This study provides new insights into the pathogenesis of H.pylori-induced onset of T2DM.

Identification and Validation of Vascular-Associated Biomarkers for the Prognosis and Potential Pathogenesis of Hypertension Using Comprehensive Bioinformatics Methods

Background: Hypertension, also known as increased blood pressure, is a phenomenon in which blood flows in blood vessels and causes persistently higher-than-normal pressure on the vessel wall. The identification of novel prognostic and pathogenesis biomarkers plays a key role in the management of hypertension. Methods: The GSE7483 and GSE75815 datasets from the gene expression omnibus (GEO) database were used to identify the genes associated with hypertension that were differentially expressed genes (DEGs). The functional role of the DEGs was elucidated by gene body (GO) enrichment analysis. In addition, we performed an immune infiltration assay and GSEA on the DEGs of hypertensive patients and verified the expression of novel DEGs in the blood of hypertensive patients by RT-qPCR. Results: A total of 267 DEGs were identified from the GEO database. GO analysis revealed that these genes were associated mainly with biological processes such as fibroblast proliferation, cell structural organization, extracellular matrix organization, vasculature development regulation, and angiogenesis. We identified five possible biomarkers, Ecm1, Sparc, Sphk1, Thbsl, and Mecp2, which correlate with vascular development and angiogenesis characteristic of hypertension by bioinformatics, and explored the clinical expression levels of these genes by RT-qPCR, and found that Sparc, Sphk1, and Thbs1 showed significant up-regulation, in agreement with the results of the bioinformatics analysis. Conclusion: Our study suggested that Sparc, Sphk1 and Thbs1 may be potential novel biomarkers for the diagnosis, treatment and prognosis of hypertension and that they are involved in the regulation of vascular development and angiogenesis in hypertension.

Are there tumor suppressor genes on chromosome 4p in sporadic colorectal carcinoma?

AIM: To study the candidate tumor suppressor genes (TSG) on chromosome 4p by detecting the high frequency of loss of heterozygosity (LOH) in sporadic colorectal carcinoma in Chinese patients.METHODS: Seven fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by PCR. PCR products were eletrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis. The same procedure was performed by the other six microsatellite markers spanning D4S3013 locus to make further detailed deletion mapping. Comparison between LOH frequency and clinicopathological factors was performed by χ2 test.RESULTS: Data were collected from all informative loci. The average LOH frequency on 4p was 24.25%, and 42.3% and 35.62% on D4S405 and D4S3013 locus, respectively. Adjacent markers of D4S3013 displayed a low LOH frequency (< 30%) by detailed deletion mapping. Significant opposite difference was observed between LOH frequency and tumor diameter on D4S412 and D4S1546 locus (0% vs 16.67%, P = 0.041; 54.55% vs 11.11%, P = 0.034, respectively). On D4S403 locus, LOH was significantly associated with tumor gross pattern (11.11%, 0, 33.33%, P = 0.030). No relationship was detected on other loci compared with clinicopathologial features.CONCLUSION: By deletion mapping, two obvious high frequency LOH regions spanning D4S3013 (4p15.2) and D4S405 (4p14) locus are detected. Candidate TSG, which is involved in carcinogenesis and progression of sporadic colorectal carcinoma on chromosome 4p, may be located between D4S3017 and D4S2933 (about 1.7 cm).