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

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  • Yeager, Meredith
    • Other Affiliation: Core Genotyping Facility, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4605, USA; Intramural Research Support Program, SAIC-Frederick, NCI-FCRDC, Frederick, Maryland 21702, USA
  • Langerød, Anita
    • Other Affiliation: Department of Genetics, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet Medical Center, Montebello, 0310 Oslo, Norway
  • Børresen-Dale, Anne-Lise
    • Other Affiliation: Department of Genetics, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet Medical Center, Montebello, 0310 Oslo, Norway; Medical Faculty, University of Oslo, 0316 Oslo, Norway
  • Perou, Charles
    • Affiliation: School of Medicine, Department of Genetics, Department of Pathology and Laboratory Medicine, N.C. Cancer Hospital, UNC Lineberger Comprehensive Cancer Center
  • Strausberg, Robert L
    • Other Affiliation: J Craig Venter Institute, Medical Center Drive, Rockville, Maryland 20850, USA
  • Gerhard, Daniela S
    • Other Affiliation: Office of Cancer Genomics, National Cancer Institute, NIH, Bethesda, Maryland 20892, USA
  • Kristensen, Vessela
    • Other Affiliation: Section of Genomic Variation, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4605, USA; >Department of Genetics, Institute for Cancer Research, Rikshospitalet-Radiumhospitalet Medical Center, Montebello, 0310 Oslo, Norway; Medical Faculty, University of Oslo, 0316 Oslo, Norway
  • Kaaresen, Rolf
    • Other Affiliation: Department of Surgery, Ullevål University Hospital, 0407 Oslo, Norway
  • Llaca, Victor
    • Other Affiliation: Intramural Research Support Program, SAIC-Frederick, NCI-FCRDC, Frederick, Maryland 21702, USA
  • Presswalla, Shafaq
    • Other Affiliation: Core Genotyping Facility, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4605, USA; Intramural Research Support Program, SAIC-Frederick, NCI-FCRDC, Frederick, Maryland 21702, USA
  • Burdett, Laurie
    • Other Affiliation: Core Genotyping Facility, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4605, USA; Intramural Research Support Program, SAIC-Frederick, NCI-FCRDC, Frederick, Maryland 21702, USA
  • Chanock, Stephen J
    • Other Affiliation: Section of Genomic Variation, Pediatric Oncology Branch, Center for Cancer Research; Core Genotyping Facility, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4605, USA
Abstract
  • Abstract 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.
Date of publication
Identifier
  • doi:10.1186/bcr1637
  • 17224074
Resource type
  • Article
Rights statement
  • In Copyright
Rights holder
  • Stephen J Chanock et al.; licensee BioMed Central Ltd.
License
Journal title
  • Breast Cancer Research
Journal volume
  • 9
Journal issue
  • 1
Page start
  • R5
Language
  • English
Is the article or chapter peer-reviewed?
  • Yes
ISSN
  • 1465-5411
Bibliographic citation
  • Breast Cancer Research. 2007 Jan 16;9(1):R5
Access
  • Open Access
Publisher
  • BioMed Central Ltd
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