The retinoblastoma gene undergoes rearrangements in BRCA1-deficient basal-like breast cancer.

Summary, in English

Breast tumors from BRCA1 germ line mutation carriers typically exhibit features of the basal-like molecular subtype. However, the specific genes recurrently mutated as a consequence of BRCA1 dysfunction have not been fully elucidated. In this study, we utilized gene expression profiling to molecularly subtype 577 breast tumors, including 72 breast tumors from BRCA1/2 mutation carriers. Focusing on the RB1 locus, we analyzed 33 BRCA1-mutated, 36 BRCA2-mutated and 48 non-BRCA1/2-mutated breast tumors using a custom-designed high-density oligomicroarray covering the RB1 gene. We found a strong association between the basal-like subtype and BRCA1-mutated breast tumors and the luminal B subtype and BRCA2-mutated breast tumors. RB1 was identified as a major target for genomic disruption in tumors arising in BRCA1 mutation carriers and in sporadic tumors with BRCA1 promoter-methylation, but rarely in other breast cancers. Homozygous deletions, intragenic breaks, or microdeletions were found in 33% of BRCA1-mutant tumors, 36% of BRCA1 promoter-methylated basal-like tumors, 13% of non-BRCA1 deficient basal-like tumors, and 3% of BRCA2-mutated tumors. In conclusion, RB1 was frequently inactivated by gross gene disruption in BRCA1-related hereditary breast cancer and BRCA1-methylated sporadic basal-like breast cancer, but rarely in BRCA2-hereditary breast cancer and non-BRCA1-deficient sporadic breast cancers. Together, our findings demonstrate the existence of genetic heterogeneity within the basal-like breast cancer subtype that is based upon BRCA1-status.

• Author: Göran B Jönsson; Johan Staaf; Johan Vallon-Christersson; Markus Ringnér; Sofia Gruvberger; Lao Saal; Karolina Holm; Cecilia Hegardt; Adalgeir Arason; Rainer Fagerholm; Camilla Olsson; Dorthe Grabau; Ellinor Johnsson; Kristina Lövgren; Linda Magnusson; Paivi Heikkilä; Bjarni A Agnarsson; Oskar Th Johannsson; Per Malmström; Mårten Fernö; Håkan Olsson; Niklas Loman; Heli Nevanlinna; Rosa Bjork Barkardottir; Åke Borg
• Department/s: Breastcancer-genetics; Tumor microenvironment; Division of Hematology and Transfusion Medicine; Division of Clinical Genetics; Familial Breast Cancer; EpiHealth: Epidemiology for Health; BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
• Publishing year: 2012
• Language: English
• Pages: 4028-4036
• Publication/Series: Cancer Research
• Volume: 72
• Issue: 16
• Links: http://www.ncbi.nlm.nih.gov/pubmed/22706203?dopt=Abstract; http://dx.doi.org/10.1158/0008-5472.CAN-12-0097
• Document type: Journal article
• Publisher: American Association for Cancer Research Inc.
• Topic: Cancer and Oncology
• Status: Published
• Research group: Familial Breast Cancer
• ISBN/ISSN/Other: ISSN: 1538-7445