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

  • 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
Publishing year: 2012
Language: English
Pages: 4028-4036
Publication/Series: Cancer Research
Volume: 72
Issue: 16
Document type: Journal article
Publisher: American Association for Cancer Research Inc.

Abstract 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.


  • Cancer and Oncology


  • CREATE Health
  • Familial Breast Cancer
  • ISSN: 1538-7445
Markus Ringnér
E-mail: markus [dot] ringner [at] biol [dot] lu [dot] se

Research engineer

Molecular Cell Biology


Sölvegatan 35, Lund