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Analysis of the 10q11 cancer risk locus implicates MSMB and NCOA4 in human prostate tumorigenesis
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نویسنده
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pomerantz m.m. ,shrestha y. ,flavin r.j. ,regan m.m. ,penney k.l. ,mucci l.a. ,stampfer m.j. ,hunter d.j. ,chanock s.j. ,schafer e.j. ,chan j.a. ,tabernero j. ,baselga j. ,richardson a.l. ,loda m. ,oh w.k. ,kantoff p.w. ,hahn w.c. ,freedman m.l.
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منبع
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plos genetics - 2010 - دوره : 6 - شماره : 11
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چکیده
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Genome-wide association studies (gwas) have established a variant,rs10993994,on chromosome 10q11 as being associated with prostate cancer risk. since the variant is located outside of a protein-coding region,the target genes driving tumorigenesis are not readily apparent. two genes nearest to this variant,msmb and ncoa4,are strong candidates for mediating the effects of rs109939934. in a cohort of 180 individuals,we demonstrate that the rs10993994 risk allele is associated with decreased expression of two msmb isoforms in histologically normal and malignant prostate tissue. in addition,the risk allele is associated with increased expression of five ncoa4 isoforms in histologically normal prostate tissue only. no consistent association with either gene is observed in breast or colon tissue. in conjunction with these findings,suppression of msmb expression or ncoa4 overexpression promotes anchorage-independent growth of prostate epithelial cells,but not growth of breast epithelial cells. these data suggest that germline variation at chromosome 10q11 contributes to prostate cancer risk by influencing expression of at least two genes. more broadly,the findings demonstrate that disease risk alleles may influence multiple genes,and associations between genotype and expression may only be observed in the context of specific tissue and disease states.
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آدرس
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department of medical oncology,dana-farber cancer institute,boston,ma,united states,department of medicine,brigham and women's hospital and harvard medical school,boston,ma, United States, department of medical oncology,dana-farber cancer institute,boston,ma,united states,center for cancer genome discovery,dana-farber cancer institute,boston,ma,united states,broad institute of harvard and massachusetts institute of technology,cambridge,ma, United States, center for molecular oncologic pathology,dana-farber cancer institute,brigham and women's hospital,boston,ma, United States, department of biostatistics and computational biology,dana-farber cancer institute and harvard medical school,boston,ma, United States, department of epidemiology,harvard school of public health,boston,ma, United States, department of epidemiology,harvard school of public health,boston,ma,united states,channing laboratory,department of medicine,brigham and women's hospital and harvard medical school,boston,ma, United States, department of epidemiology,harvard school of public health,boston,ma,united states,channing laboratory,department of medicine,brigham and women's hospital and harvard medical school,boston,ma,united states,department of nutrition,harvard school of public health,boston,ma, United States, department of epidemiology,harvard school of public health,boston,ma,united states,channing laboratory,department of medicine,brigham and women's hospital and harvard medical school,boston,ma,united states,department of nutrition,harvard school of public health,boston,ma, United States, division of cancer epidemiology and genetics,national cancer institute,national institutes of health,bethesda,md, United States, department of medical oncology,dana-farber cancer institute,boston,ma,united states,center for cancer genome discovery,dana-farber cancer institute,boston,ma,united states,broad institute of harvard and massachusetts institute of technology,cambridge,ma, United States, department of pathology and laboratory medicine,university of calgary,calgary,ab, Canada, vall d'hebron institute of oncology,vall d'hebron university hospital,barcelona, Spain, vall d'hebron institute of oncology,vall d'hebron university hospital,barcelona, Spain, department of pathology,brigham and women's hospital and harvard medical school,boston,ma, United States, department of medical oncology,dana-farber cancer institute,boston,ma,united states,center for cancer genome discovery,dana-farber cancer institute,boston,ma,united states,broad institute of harvard and massachusetts institute of technology,cambridge,ma,united states,center for molecular oncologic pathology,dana-farber cancer institute,brigham and women's hospital,boston,ma,united states,department of pathology,brigham and women's hospital and harvard medical school,boston,ma, United States, tisch cancer institute,mount sinai school of medicine,new york,ny, United States, department of medical oncology,dana-farber cancer institute,boston,ma,united states,department of medicine,brigham and women's hospital and harvard medical school,boston,ma, United States, department of medical oncology,dana-farber cancer institute,boston,ma,united states,department of medicine,brigham and women's hospital and harvard medical school,boston,ma,united states,center for cancer genome discovery,dana-farber cancer institute,boston,ma,united states,broad institute of harvard and massachusetts institute of technology,cambridge,ma, United States, department of medical oncology,dana-farber cancer institute,boston,ma,united states,center for cancer genome discovery,dana-farber cancer institute,boston,ma,united states,broad institute of harvard and massachusetts institute of technology,cambridge,ma, United States
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Authors
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