Journal article

Clinical classification of BRCA1 and BRCA2 DNA sequence variants: The value of cytokeratin profiles and evolutionary analysis - A report from the kConFab investigators

Amanda B Spurdle, Sunil R Lakhani, Sue Healey, Suzanne Parry, Leonard M Da Silva, Ross Brinkworth, John L Hopper, Melissa A Brown, Davit Babikyan, Georgia Chenevix-Trench, Sean V Tavtigian, David E Goldgar

JOURNAL OF CLINICAL ONCOLOGY | AMER SOC CLINICAL ONCOLOGY | Published : 2008

Abstract

PURPOSE: Rare missense substitutions and in-frame deletions of BRCA1 and BRCA2 genes present a challenge for genetic counseling of individuals carrying such unclassified variants. We assessed the value of tumor immunohistochemical markers in conjunction with genetic and evolutionary approaches for investigating the clinical significance of unclassified variants. PATIENTS AND METHODS: We studied 10 BRCA1 and 12 BRCA2 variants identified in Australian families with breast cancer. Analyses assumed a prior probability based on revised cross-species sequence alignment methods assessing amino acid evolutionary conservation and position, combined with likelihoods from data on co-occurrence with pat..

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