Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

The retinoblastoma gene is targeted for rearrangements in BRCA1-deficient basal-like breast cancer.

ABSTRACT: 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 73 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 addition, 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. Gene expression profiling of breast tumors. Dual color common reference gene expression study using 55K oligonucleotide microarrays.

ORGANISM(S): Homo sapiens

SUBMITTER: Åke Borg

PROVIDER: E-GEOD-25307 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

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

Jönsson Göran G Staaf Johan J Vallon-Christersson Johan J Ringnér Markus M Gruvberger-Saal Sofia K SK Saal Lao H LH Holm Karolina K Hegardt Cecilia C Arason Adalgeir A Fagerholm Rainer R Persson Camilla C Grabau Dorthe D Johnsson Ellinor E Lövgren Kristina K Magnusson Linda L Heikkilä Päivi P Agnarsson Bjarni A BA Johannsson Oskar T OT Malmström Per P Fernö Mårten M Olsson Håkan H Loman Niklas N Nevanlinna Heli H Barkardottir Rosa B RB Borg Åke Å

Cancer research 20120615 16

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 used gene expression profiling to molecularly subtype 577 breast tumors, including 73 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 ...[more]

PMID: 22706203

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Dataset Information

The retinoblastoma gene is targeted for rearrangements in BRCA1-deficient basal-like breast cancer.

Publications

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

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