Somatic sequence alterations in twenty-one genes selected by expression profile analysis of breast carcinomas

被引:22
作者
Chanock, Stephen J. [1 ]
Burdett, Laurie
Yeager, Meredith
Llaca, Victor
Langerod, Anita
Presswalla, Shafaq
Kaaresen, Rolf
Strausberg, Robert L.
Gerhard, Daniela S.
Kristensen, Vessela
Perou, Charles M.
Borresen-Dale, Anne-Lise
机构
[1] NCI, Canc Res Ctr, Pediat Oncol Branch, Sect Genom Variat,NIH, Bethesda, MD 20892 USA
[2] NCI, Core Genotyping Facil, NIH, Bethesda, MD 20892 USA
[3] NCI, Frederick Canc Res & Dev Ctr, SAID Frederick, Intramural Res Support Program, Frederick, MD 21702 USA
[4] Norwegian Radium Hosp, Rikshosp, Med Ctr, Inst Canc Res,Dept Genet, N-0310 Oslo, Norway
[5] Univ Oslo, Ulleval Hosp, Dept Surg, N-0407 Oslo, Norway
[6] J Craig Venter Inst, Rockville, MD 20850 USA
[7] NCI, Off Canc Genom, Bethesda, MD 20892 USA
[8] Univ Oslo, Fac Med, N-0316 Oslo, Norway
[9] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Genet, Chapel Hill, NC 27599 USA
[10] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Pathol, Chapel Hill, NC 27599 USA
[11] Univ N Carolina, Lineberger Comprehens Canc Ctr, Dept Lab Med, Chapel Hill, NC 27599 USA
关键词
D O I
10.1186/bcr1637
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Introduction Genomic alterations have been observed in breast carcinomas that affect the capacity of cells to regulate proliferation, signaling, and metastasis. Re-sequence studies have investigated candidate genes based on prior genetic observations ( changes in copy number or regions of genetic instability) or other laboratory observations and have defined critical somatic mutations in genes such as TP53 and PIK3CA. Methods We have extended the paradigm and analyzed 21 genes primarily identified by expression profiling studies, which are useful for breast cancer subtyping and prognosis. This study conducted a bidirectional re-sequence analysis of all exons and 5', 3', and evolutionarily conserved regions ( spanning more than 16 megabases) in 91 breast tumor samples. Results Eighty-seven unique somatic alterations were identified in 16 genes. Seventy-eight were single base pair alterations, of which 23 were missense mutations; 55 were distributed across conserved intronic regions or the 5' and 3' regions. There were nine insertion/deletions. Because there is no a priori way to predict whether any one of the identified synonymous and noncoding somatic alterations disrupt function, analysis unique to each gene will be required to establish whether it is a tumor suppressor gene or whether there is no effect. In five genes, no somatic alterations were observed. Conclusion The study confirms the value of re-sequence analysis in cancer gene discovery and underscores the importance of characterizing somatic alterations across genes that are related not only by function, or functional pathways, but also based upon expression patterns.
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页数:9
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