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BRCA1-like signatur...
BRCA1-like signature in triple negative breast cancer: Molecular and clinical characterization reveals subgroups with therapeutic potential.
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Severson, Tesa M (författare)
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Peeters, Justine (författare)
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Majewski, Ian (författare)
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Michaut, Magali (författare)
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Bosma, Astrid (författare)
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Schouten, Philip C (författare)
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Chin, Suet-Feung (författare)
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Pereira, Bernard (författare)
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Goldgraben, Mae A (författare)
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Bismeijer, Tycho (författare)
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Kluin, Roelof J C (författare)
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Muris, Jettie J F (författare)
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- Jirström, Karin (författare)
- Lund University,Lunds universitet,Tumörmikromiljö,Sektion I,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Tumor microenvironment,Section I,Department of Clinical Sciences, Lund,Faculty of Medicine
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Kerkhoven, Ron M (författare)
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Wessels, Lodewyk (författare)
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Caldas, Carlos (författare)
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Bernards, René (författare)
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Simon, Iris M (författare)
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Linn, Sabine (författare)
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(creator_code:org_t)
- 2015-05-07
- 2015
- Engelska.
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Ingår i: Molecular Oncology. - : Wiley. - 1574-7891. ; 9:8, s. 1528-1538
- Relaterad länk:
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http://www.ncbi.nlm....
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http://dx.doi.org/10...
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https://doi.org/10.1...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
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- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Severson, Tesa M
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Peeters, Justine
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Majewski, Ian
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Michaut, Magali
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Bosma, Astrid
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Schouten, Philip ...
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visa fler...
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Chin, Suet-Feung
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Pereira, Bernard
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Goldgraben, Mae ...
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Bismeijer, Tycho
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Kluin, Roelof J ...
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Muris, Jettie J ...
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Jirström, Karin
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Kerkhoven, Ron M
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Wessels, Lodewyk
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Caldas, Carlos
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Bernards, René
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Simon, Iris M
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Linn, Sabine
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visa färre...
- Om ämnet
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- MEDICIN OCH HÄLSOVETENSKAP
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MEDICIN OCH HÄLS ...
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och Klinisk medicin
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och Cancer och onkol ...
- Artiklar i publikationen
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Molecular Oncolo ...
- Av lärosätet
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Lunds universitet