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Genomic signature of BRCA1 deficiency in sporadic basal‐like breast tumors

Genomic signature of BRCA1 deficiency in sporadic basal‐like breast tumors About 10–20% of all breast carcinomas show a basal‐like phenotype, while ∼ 90% of breast tumors from BRCA1‐mutation carriers are of this subtype. There is growing evidence that BRCA1‐mutated tumors are not just a specific subset of the basal‐like tumors, but that (the majority of) basal‐like tumors show a dysfunctional BRCA1 pathway. This has major treatment implications, because emerging regimens specifically targeting DNA repair mechanisms would then be most effective against these tumors. To further understand the involvement of BRCA1 deficiency in sporadic basal‐like tumors, we investigated 41 basal‐like tumors for BRCA1 mRNA expression by quantitative real‐time polymerase chain reaction, BRCA1 promoter methylation, their genomic profile by array‐CGH, and gene expression levels by whole genome expression arrays. Array‐CGH results were compared to those of 34 proven BRCA1‐mutated tumors. Basal‐like tumors were subdivided into two equal groups: deficient and proficient in BRCA1 gene expression. The chromosomal makeup of BRCA1 deficient sporadic basal‐like tumors was similar to that of BRCA1‐mutated tumors. BRCA1 proficient sporadic basal‐like tumors were more similar to nonbasal‐like tumors. Only half of the basal‐like breast tumors are actually deficient in BRCA1 expression. Gain of chromosome arm 3q is a marker for BRCA1 deficiency in hereditary and sporadic breast tumors. © 2010 Wiley‐Liss, Inc. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Genes, Chromosomes and Cancer Wiley

Genomic signature of BRCA1 deficiency in sporadic basal‐like breast tumors

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References (55)

Publisher
Wiley
Copyright
Copyright © 2010 Wiley‐Liss, Inc.
ISSN
1045-2257
eISSN
1098-2264
DOI
10.1002/gcc.20833
pmid
21104783
Publisher site
See Article on Publisher Site

Abstract

About 10–20% of all breast carcinomas show a basal‐like phenotype, while ∼ 90% of breast tumors from BRCA1‐mutation carriers are of this subtype. There is growing evidence that BRCA1‐mutated tumors are not just a specific subset of the basal‐like tumors, but that (the majority of) basal‐like tumors show a dysfunctional BRCA1 pathway. This has major treatment implications, because emerging regimens specifically targeting DNA repair mechanisms would then be most effective against these tumors. To further understand the involvement of BRCA1 deficiency in sporadic basal‐like tumors, we investigated 41 basal‐like tumors for BRCA1 mRNA expression by quantitative real‐time polymerase chain reaction, BRCA1 promoter methylation, their genomic profile by array‐CGH, and gene expression levels by whole genome expression arrays. Array‐CGH results were compared to those of 34 proven BRCA1‐mutated tumors. Basal‐like tumors were subdivided into two equal groups: deficient and proficient in BRCA1 gene expression. The chromosomal makeup of BRCA1 deficient sporadic basal‐like tumors was similar to that of BRCA1‐mutated tumors. BRCA1 proficient sporadic basal‐like tumors were more similar to nonbasal‐like tumors. Only half of the basal‐like breast tumors are actually deficient in BRCA1 expression. Gain of chromosome arm 3q is a marker for BRCA1 deficiency in hereditary and sporadic breast tumors. © 2010 Wiley‐Liss, Inc.

Journal

Genes, Chromosomes and CancerWiley

Published: Feb 1, 2011

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