Absence of genomic BRCA1 and BRCA2 rearrangements in Ashkenazi breast and ovarian cancer families Journal Article


Authors: Stadler, Z. K.; Saloustros, E.; Hansen, N. A. L.; Schluger, A. E.; Kauff, N. D.; Offit, K.; Robson, M. E.
Article Title: Absence of genomic BRCA1 and BRCA2 rearrangements in Ashkenazi breast and ovarian cancer families
Abstract: A substantial proportion of Ashkenazi Jewish (AJ) breast and ovarian cancer families carry one of three founder mutations in BRCA1 (185delAG, 5382InsC) and BRCA2 (6174delT). Non-founder mutations are identified in another 2-4% of such families. The extent to which major genomic rearrangements in BRCA contribute to breast and ovarian cancer in the Ashkenazim is not well understood. We identified AJ individuals with breast and/or ovarian cancer undergoing hereditary breast/ovarian cancer risk assessment since 2006 without evidence of a deleterious mutation on BRCA gene sequencing who were screened for major gene rearrangements in BRCA1 and BRCA2. For each proband, the pre-test probability of identifying a deleterious BRCA mutation was estimated using the Myriad II model. We identified 108 affected individuals who underwent large rearrangement testing (80 breast cancer, 19 ovarian cancer, nine both breast and ovarian cancer). The mean estimated AJ specific pre-test probability of a deleterious mutation in BRCA1 and BRCA2 was 24.7% (range: 4.4-88.9%). No genomic rearrangements were identified in either the entire group or in the 26 subjects with pre-test mutation prevalence estimates exceeding 30%. Major gene rearrangements involving the BRCA1 and BRCA2 genes appear to contribute little to the burden of inherited predisposition to breast and ovarian cancer in the Ashkenazim. © 2010 Springer Science+Business Media, LLC.
Keywords: adult; controlled study; middle aged; gene mutation; major clinical study; mutation; cancer risk; ovarian neoplasms; phenotype; genetic predisposition to disease; ovary cancer; breast cancer; genetic association; risk factors; mutational analysis; breast neoplasms; brca1 protein; brca2 protein; risk assessment; carcinogenesis; pedigree; gene rearrangement; amino acid sequence; probability; new york city; familial cancer; high risk population; genetic predisposition; brca; founder effect; jews; jew; breast neoplasms, male; rearrangements; founder mutations; jewish
Journal Title: Breast Cancer Research and Treatment
Volume: 123
Issue: 2
ISSN: 0167-6806
Publisher: Springer  
Date Published: 2010-09-01
Start Page: 581
End Page: 585
Language: English
DOI: 10.1007/s10549-010-0818-y
PUBMED: 20221693
PROVIDER: scopus
DOI/URL:
Notes: --- - "Export Date: 20 April 2011" - "CODEN: BCTRD" - "Source: Scopus"
Altmetric Score
MSK Authors
  1. Kenneth Offit
    519 Offit
  2. Mark E Robson
    368 Robson
  3. Noah Kauff
    122 Kauff
  4. Zsofia Kinga Stadler
    152 Stadler
  5. Nichole Hansen
    9 Hansen