Functional evaluation and cancer risk assessment of BRCA2 unclassified variants

Kangjian Wu, Shannon R. Hinson, Akihiro Ohashi, Daniel Farrugia, Patricia Wendt, Sean V. Tavtigian, Amie Deffenbaugh, David Goldgar, Fergus J. Couch

Research output: Contribution to journalArticle

90 Scopus citations

Abstract

The influence of germ line BRCA2 unclassified variants (UCV), including missense mutations and in-frame deletions and insertions on BRCA2 function and on cancer risk, has not been defined although these mutations account for 43% of all identified BRCA2 sequence alterations. To investigate the effects of UCVs on BRCA2 function, we compared mutant and wild-type forms of BRCA2 using assays of cellular survival and viability, homologous recombination repair, and genome instability. We confirm that the effects of known deleterious mutations can be distinguished from neutral polymorphisms and wild-type BRCA2 in these assays, and we characterize the influence of a series of UCVs on BRCA2 function. We also describe how the results from the assays can be combined with data from analysis of cosegregation of the UCVs with cancer, co-occurrence of the UCVs with other deleterious mutations, and interspecies sequence variation in a comprehensive framework in an effort to better distinguish between disease predisposing and neutral UCVs. This combined approach represents a useful means of addressing the functional significance and cancer relevance of UCVs in BRCA2.

Original languageEnglish (US)
Pages (from-to)417-426
Number of pages10
JournalCancer research
Volume65
Issue number2
StatePublished - Jan 15 2005

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Wu, K., Hinson, S. R., Ohashi, A., Farrugia, D., Wendt, P., Tavtigian, S. V., Deffenbaugh, A., Goldgar, D., & Couch, F. J. (2005). Functional evaluation and cancer risk assessment of BRCA2 unclassified variants. Cancer research, 65(2), 417-426.