Molecular profiles of BRCA1-mutated and matched sporadic breast tumours: relation with clinico-pathological features

About 5-10% of breast cancers are hereditary; a genetically and clinically heterogeneous disease in which several susceptibility genes, including BRCA 1, have been identified. While distinct tumour features can be used to esti mate the likelihood that a breast tumour is caused by a BRCA1 germline muta tion it is not yet possible to categorize a BRCA1 mutated tumour. The aim o f the present study is to molecularly classify BRCA1 mutated breast cancers by resolving gene expression patterns of BRCA1 and matched sporadic surgic al breast tumour specimens. The expression profiles of 6 frozen breast tumo ur tissues with a proven BRCA1 gene mutation were weighed against those fro m 12 patients without a known family history but who had similar clinico-pa thological characteristics. In addition two fibroblast cultures, the breast cancer cell-line HCC1937 and its corresponding B-lymphoblastoid cell line (heterozygous for mutation BRCA1 5382insC) and an epithelial ovarian cancer cell line (A2780) were studied. Using a high density membrane based array for screening of RNA isolated from these samples and standard algorithms an d software, we were able to distinguish subgroups of sporadic cases and a g roup consisting mainly of BRCA1-mutated breast tumours. Furthermore this pi lot analysis revealed a gene cluster that differentially expressed genes re lated to cell substrate formation, adhesion, migration and cell organizatio n in BRCA1-mutated tumours compared to sporadic breast tumours. (C) 2001 Ca ncer Research Campaign.