BRCA1-like signature in triple negative breast cancer: Molecular and clinical characterization reveals subgroups with therapeutic potential.
(2015) In Molecular Oncology 9(8). p.1528-1538- Abstract
- Triple negative (TN) breast cancers make up some 15% of all breast cancers. Approximately 10-15% are mutant for the tumor suppressor, BRCA1. BRCA1 is required for homologous recombination-mediated DNA repair and deficiency results in genomic instability. BRCA1-mutated tumors have a specific pattern of genomic copy number aberrations that can be used to classify tumors as BRCA1-like or non-BRCA1-like. BRCA1 mutation, promoter methylation, BRCA1-like status and genome-wide expression data was determined for 112 TN breast cancer samples with long-term follow-up. Mutation status for 21 known DNA repair genes and PIK3CA was assessed. Gene expression and mutation frequency in BRCA1-like and non-BRCA1-like tumors were compared. Multivariate... (More)
- Triple negative (TN) breast cancers make up some 15% of all breast cancers. Approximately 10-15% are mutant for the tumor suppressor, BRCA1. BRCA1 is required for homologous recombination-mediated DNA repair and deficiency results in genomic instability. BRCA1-mutated tumors have a specific pattern of genomic copy number aberrations that can be used to classify tumors as BRCA1-like or non-BRCA1-like. BRCA1 mutation, promoter methylation, BRCA1-like status and genome-wide expression data was determined for 112 TN breast cancer samples with long-term follow-up. Mutation status for 21 known DNA repair genes and PIK3CA was assessed. Gene expression and mutation frequency in BRCA1-like and non-BRCA1-like tumors were compared. Multivariate survival analysis was performed using the Cox proportional hazards model. BRCA1 germline mutation was identified in 10% of patients and 15% of tumors were BRCA1 promoter methylated. Fifty-five percent of tumors classified as BRCA1-like. The functions of genes significantly up-regulated in BRCA1-like tumors included cell cycle and DNA recombination and repair. TP53 was found to be frequently mutated in BRCA1-like (P < 0.05), while PIK3CA was frequently mutated in non-BRCA1-like tumors (P < 0.05). A significant association with worse prognosis was evident for patients with BRCA1-like tumors (adjusted HR = 3.32, 95% CI = 1.30-8.48, P = 0.01). TN tumors can be further divided into two major subgroups, BRCA1-like and non-BRCA1-like with different mutation and expression patterns and prognoses. Based on these molecular patterns, subgroups may be more sensitive to specific targeted agents such as PI3K or PARP inhibitors. (Less)
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https://lup.lub.lu.se/record/5442486
- author
- Severson, Tesa M
; Peeters, Justine
; Majewski, Ian
; Michaut, Magali
; Bosma, Astrid
; Schouten, Philip C
; Chin, Suet-Feung
; Pereira, Bernard
; Goldgraben, Mae A
; Bismeijer, Tycho
; Kluin, Roelof J C
; Muris, Jettie J F
; Jirström, Karin
LU
; Kerkhoven, Ron M
; Wessels, Lodewyk
; Caldas, Carlos
; Bernards, René
; Simon, Iris M
and Linn, Sabine
(Less) - organization
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Molecular Oncology
- volume
- 9
- issue
- 8
- pages
- 1528 - 1538
- publisher
- Elsevier
- external identifiers
-
- pmid:26004083
- wos:000362308500003
- scopus:84942193303
- pmid:26004083
- ISSN
- 1574-7891
- DOI
- 10.1016/j.molonc.2015.04.011
- language
- English
- LU publication?
- yes
- additional info
- The information about affiliations in this record was updated in December 2015. The record was previously connected to the following departments: Pathology, (Lund) (013030000)
- id
- a9e7d4bc-231c-4f64-95e2-a4137c9ceff2 (old id 5442486)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/26004083?dopt=Abstract
- date added to LUP
- 2016-04-01 10:59:49
- date last changed
- 2024-01-07 06:17:56
@article{a9e7d4bc-231c-4f64-95e2-a4137c9ceff2,
abstract = {{Triple negative (TN) breast cancers make up some 15% of all breast cancers. Approximately 10-15% are mutant for the tumor suppressor, BRCA1. BRCA1 is required for homologous recombination-mediated DNA repair and deficiency results in genomic instability. BRCA1-mutated tumors have a specific pattern of genomic copy number aberrations that can be used to classify tumors as BRCA1-like or non-BRCA1-like. BRCA1 mutation, promoter methylation, BRCA1-like status and genome-wide expression data was determined for 112 TN breast cancer samples with long-term follow-up. Mutation status for 21 known DNA repair genes and PIK3CA was assessed. Gene expression and mutation frequency in BRCA1-like and non-BRCA1-like tumors were compared. Multivariate survival analysis was performed using the Cox proportional hazards model. BRCA1 germline mutation was identified in 10% of patients and 15% of tumors were BRCA1 promoter methylated. Fifty-five percent of tumors classified as BRCA1-like. The functions of genes significantly up-regulated in BRCA1-like tumors included cell cycle and DNA recombination and repair. TP53 was found to be frequently mutated in BRCA1-like (P < 0.05), while PIK3CA was frequently mutated in non-BRCA1-like tumors (P < 0.05). A significant association with worse prognosis was evident for patients with BRCA1-like tumors (adjusted HR = 3.32, 95% CI = 1.30-8.48, P = 0.01). TN tumors can be further divided into two major subgroups, BRCA1-like and non-BRCA1-like with different mutation and expression patterns and prognoses. Based on these molecular patterns, subgroups may be more sensitive to specific targeted agents such as PI3K or PARP inhibitors.}},
author = {{Severson, Tesa M and Peeters, Justine and Majewski, Ian and Michaut, Magali and Bosma, Astrid and Schouten, Philip C and Chin, Suet-Feung and Pereira, Bernard and Goldgraben, Mae A and Bismeijer, Tycho and Kluin, Roelof J C and Muris, Jettie J F and Jirström, Karin and Kerkhoven, Ron M and Wessels, Lodewyk and Caldas, Carlos and Bernards, René and Simon, Iris M and Linn, Sabine}},
issn = {{1574-7891}},
language = {{eng}},
number = {{8}},
pages = {{1528--1538}},
publisher = {{Elsevier}},
series = {{Molecular Oncology}},
title = {{BRCA1-like signature in triple negative breast cancer: Molecular and clinical characterization reveals subgroups with therapeutic potential.}},
url = {{http://dx.doi.org/10.1016/j.molonc.2015.04.011}},
doi = {{10.1016/j.molonc.2015.04.011}},
volume = {{9}},
year = {{2015}},
}