Family-specific, novel, deleterious germline variants provide a rich resource to identify genetic predispositions for BRCAx familial breast cancer

Hongxiu Wen, Yeong C. Kim, Carrie Snyder, Fengxia Xiao, Elizabeth A. Fleissner, Dina Becirovic, Jiangtao Luo, Bradley Downs, Simon Sherman, Kenneth H. Cowan, Henry T. Lynch, San M. Wang

Research output: Contribution to journalArticle

11 Scopus citations

Abstract

Background: Genetic predisposition is the primary risk factor for familial breast cancer. For the majority of familial breast cancer, however, the genetic predispositions remain unknown. All newly identified predispositions occur rarely in disease population, and the unknown genetic predispositions are estimated to reach up to total thousands. Family unit is the basic structure of genetics. Because it is an autosomal dominant disease, individuals with a history of familial breast cancer must carry the same genetic predisposition across generations. Therefore, focusing on the cases in lineages of familial breast cancer, rather than pooled cases in disease population, is expected to provide high probability to identify the genetic predisposition for each family.Methods: In this study, we tested genetic predispositions by analyzing the family-specific variants in familial breast cancer. Using exome sequencing, we analyzed three families and 22 probands with BRCAx (BRCA-negative) familial breast cancer.Results: We observed the presence of family-specific, novel, deleterious germline variants in each family. Of the germline variants identified, many were shared between the disease-affected family members of the same family but not found in different families, which have their own specific variants. Certain variants are putative deleterious genetic predispositions damaging functionally important genes involved in DNA replication and damaging repair, tumor suppression, signal transduction, and phosphorylation.Conclusions: Our study demonstrates that the predispositions for many BRCAx familial breast cancer families can lie in each disease family. The application of a family-focused approach has the potential to detect many new predispositions.

Original languageEnglish (US)
Article number470
JournalBMC Cancer
Volume14
Issue number1
DOIs
StatePublished - Jun 26 2014

All Science Journal Classification (ASJC) codes

  • Genetics
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'Family-specific, novel, deleterious germline variants provide a rich resource to identify genetic predispositions for BRCAx familial breast cancer'. Together they form a unique fingerprint.

  • Cite this

    Wen, H., Kim, Y. C., Snyder, C., Xiao, F., Fleissner, E. A., Becirovic, D., Luo, J., Downs, B., Sherman, S., Cowan, K. H., Lynch, H. T., & Wang, S. M. (2014). Family-specific, novel, deleterious germline variants provide a rich resource to identify genetic predispositions for BRCAx familial breast cancer. BMC Cancer, 14(1), [470]. https://doi.org/10.1186/1471-2407-14-470