A sensitive test for the detection of specific DSB repair defects in primary cells from breast cancer specimens.

Abstract	Increasing evidence indicates that breast cancer pathogenesis is linked with DNA double-strand break (DSB) repair dysfunction. This conclusion is based on advances in the study of functions of breast cancer susceptibility genes such as BRCA1 and BRCA2, on the identification of breast cancer-associated changes regarding the genetics, expression, and localization of multiple DSB repair factors, and on observations indicating enhanced radiation-induced chromosomal damage in cells from predisposed individuals and sporadic breast cancer patients. In this pilot study, we describe a sensitive method for the analysis of DSB repair functions in mammary carcinomas. Using this method we firstly document alterations in pathway-specific DSB repair activities in primary cells originating from familial as well as sporadic breast cancer. In particular, we identified increases in the mutagenic nonhomologous end joining and single-strand annealing mechanisms in sporadic breast cancers with wild-type BRCA1 and BRCA2, and, thus, similar phenotypes to tumors with mutant alleles of BRCA1 and BRCA2. This suggests that detection of error-prone DSB repair activities may be useful to extend the limits of genotypic characterization of high-risk susceptibility genes. This method may, therefore, serve as a marker for breast cancer risk assessment and, even more importantly, for the prediction of responsiveness to targeted therapies such as to inhibitors of poly(ADP-ribose)polymerase (PARP1).
Authors	Marlen Keimling, Jatinder Kaur, Sarangadhara Appala Raju Bagadi, Rolf Kreienberg, Lisa Wiesmüller, Ranju Ralhan
Journal	International journal of cancer (Int J Cancer) Vol. 123 Issue 3 Pg. 730-6 (Aug 01 2008) ISSN: 1097-0215 [Electronic] United States
PMID	18491400 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Fluorescent Dyes enhanced green fluorescent protein Green Fluorescent Proteins
Topics	Breast Neoplasms (genetics) Cell Line, Tumor DNA Breaks, Double-Stranded DNA Mutational Analysis DNA Repair Female Fluorescent Dyes Genes, BRCA1 Genes, BRCA2 Genes, p53 Genetic Predisposition to Disease Green Fluorescent Proteins Humans Immunohistochemistry Neoplastic Stem Cells

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