Regular Article

British Journal of Cancer (2001) 85, 538–545. doi:10.1054/bjoc.2001.1937 www.bjcancer.com
Published online 14 August 2001

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

E M J J Berns1, I L van Staveren1, L Verhoog1,2, A M W van de Ouweland3, M Meijer-van Gelder1, H Meijers-Heijboer3, H Portengen1, J A Foekens1, L C J Dorssers2 and J G M Klijn1

  1. 1Division of Endocrine Oncology, Department of Medical Oncology, Rotterdam Cancer Center (Daniel den Hoed Kliniek) and University Hospital Rotterdam, The Netherlands
  2. 2Department of Pathology, Erasmus University Rotterdam, The Netherlands
  3. 3Department of Clinical Genetics, Erasmus University Rotterdam, The Netherlands

Correspondence: E M J J Berns, Department of Medical Oncology, Josephine Nefkens Institute, Room Be 424, P.O. Box 1738, 3000 DR Rotterdam, The Netherlands

Received 5 October 2000; Revised 14 March 2001; Accepted 27 April 2001.

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Abstract

About 5–10% of breast cancers are hereditary; a genetically and clinically heterogeneous disease in which several susceptibility genes, including BRCA1, have been identified. While distinct tumour features can be used to estimate the likelihood that a breast tumour is caused by a BRCA1 germline mutation it is not yet possible to categorize a BRCA1 mutated tumour. The aim of the present study is to molecularly classify BRCA1 mutated breast cancers by resolving gene expression patterns of BRCA1 and matched sporadic surgical breast tumour specimens. The expression profiles of 6 frozen breast tumour tissues with a proven BRCA1 gene mutation were weighed against those from 12 patients without a known family history but who had similar clinico-pathological 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 and software, we were able to distinguish subgroups of sporadic cases and a group consisting mainly of BRCA1-mutated breast tumours. Furthermore this pilot analysis revealed a gene cluster that differentially expressed genes related to cell substrate formation, adhesion, migration and cell organization in BRCA1-mutated tumours compared to sporadic breast tumours. © 2001 Cancer Research Campaign http://www.bjcancer.com

Keywords:

BRCA1, cDNA array, breast cancer, clinical features, molecular profiles

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