Absence of truncating BRIP1 mutations in chromosome 17q-linked hereditary prostate cancer families

作者：Ray A M; Zuhlke K A; Johnson G R; Levin A M; Douglas J A; Lange E M; Cooney K A^*

来源：British Journal of Cancer, 2009, 101(12): 2043-2047.

DOI：10.1038/sj.bjc.6605433

• prostate cancer
• BRIP1
• genetic variation

BACKGROUND: In a genome-wide scan (GWS) of 175 multiplex prostate cancer (PCa) families from the University of Michigan Prostate Cancer Genetics Project (PCGP), linkage was observed to markers on chromosome 17q21-24, a region that includes two breast cancer susceptibility genes, BRCA1 and BRIP1. BRIP1 is a Fanconi anaemia gene (FANCJ) that interacts with the BRCT domain of BRCA1 and has a role in DNA damage repair. Protein truncating mutations in BRIP1 have been identified in hereditary breast and ovarian cancer families, and a recent report suggested that a recurrent truncating mutation (R798X) may have a role in PCa susceptibility.
METHODS: We examined the role of BRIP1 mutations in hereditary PCa through sequence analysis of 94 individuals from PCGP families showing linkage to 17q.
RESULTS: A total of 24 single-nucleotide polymorphisms, including 7 missense variants but no protein truncating mutations, were observed.
CONCLUSIONS: The data presented here suggest that BRIP1 truncating mutations are uncommon in PCa cases and do not account for the linkage to chromosome 17q observed in our GWS. Additional investigation is needed to determine the significance, if any, of the observed BRIP1 missense variants in hereditary PCa. British Journal of Cancer (2009) 101, 2043-2047. doi: 10.1038/sj.bjc.6605433 www.bjcancer.

• 出版日期2009-12-8