title: Somatic sequence alterations in twenty-one genes selected by expression profile analysis of breast carcinomas.
abstract: BACKGROUND
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Section of Genomic Variation, Pediatric Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892-4605, USA. chanocks@mail.nih.gov
authors.forename: Stephen J
authors.initials: SJ
authors.lastname: Chanock
authors.forename: Laurie
authors.initials: L
authors.lastname: Burdett
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.forename: Victor
authors.initials: V
authors.lastname: Llaca
authors.forename: Anita
authors.initials: A
authors.lastname: Langerød
authors.forename: Shafaq
authors.initials: S
authors.lastname: Presswalla
authors.forename: Rolf
authors.initials: R
authors.lastname: Kaaresen
authors.forename: Robert L
authors.initials: RL
authors.lastname: Strausberg
authors.forename: Daniela S
authors.initials: DS
authors.lastname: Gerhard
authors.forename: Vessela
authors.initials: V
authors.lastname: Kristensen
authors.forename: Charles M
authors.initials: CM
authors.lastname: Perou
authors.forename: Anne-Lise
authors.initials: AL
authors.lastname: Børresen-Dale
mesh_terms: D001943:Breast Neoplasms / Q000235:genetics*; D002277:Carcinoma / Q000235:genetics*; D017124:Conserved Sequence; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans