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

Stephen J Chanock12*, Laurie Burdett23, Meredith Yeager23, Victor Llaca3, Anita Langerød4, Shafaq Presswalla23, Rolf Kaaresen5, Robert L Strausberg6, Daniela S Gerhard7, Vessela Kristensen148, Charles M Perou9 and Anne-Lise Børresen-Dale48

Author Affiliations

1 Section of Genomic Variation, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4605, USA

2 Core Genotyping Facility, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4605, USA

3 Intramural Research Support Program, SAIC-Frederick, NCI-FCRDC, Frederick, Maryland 21702, USA

4 Department of Genetics, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet Medical Center, Montebello, 0310 Oslo, Norway

5 Department of Surgery, Ullevål University Hospital, 0407 Oslo, Norway

6 J Craig Venter Institute, Medical Center Drive, Rockville, Maryland 20850, USA

7 Office of Cancer Genomics, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA

8 Medical Faculty, University of Oslo, 0316 Oslo, Norway

9 Departments of Genetics and Pathology, Laboratory Medicine, Lineberger Comprehensive Cancer Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA

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Breast Cancer Research 2007, 9:R5  doi:10.1186/bcr1637

See related editorial by Dalgliesh and Futreal,

Published: 16 January 2007



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.


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.


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.


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.