Genomic hallmarks of homologous recombination deficiency in invasive breast carcinomas.
Int J Cancer
; 138(4): 891-900, 2016 Feb 15.
Article
en En
| MEDLINE
| ID: mdl-26317927
ABSTRACT
Therapeutic strategies targeting Homologous Recombination Deficiency (HRD) in breast cancer requires patient stratification. The LST (Large-scale State Transitions) genomic signature previously validated for triple-negative breast carcinomas (TNBC) was evaluated as biomarker of HRD in luminal (hormone receptor positive) and HER2-overexpressing (HER2+) tumors. The LST genomic signature related to the number of large-scale chromosomal breakpoints in SNP-array tumor profile was applied to identify HRD in in-house and TCGA sets of breast tumors, in which the status of BRCA1/2 and other genes was also investigated. In the in-house dataset, HRD was predicted in 5% (20/385) of sporadic tumors luminal or HER2+ by the LST genomic signature and the inactivation of BRCA1, BRCA2 or RAD51C confirmed this prediction in 75% (12/16) of the tested cases. In 14% (6/43) of tumors occurring in BRCA1/2 mutant carriers, the corresponding wild-type allele was retained emphasizing the importance of determining the tumor status. In the TCGA luminal and HER2+ subtypes HRD incidence was estimated at 5% (18/329, 95%CI 5-8%) and 2% (1/59, 95%CI 2-9%), respectively. In TNBC cisplatin-based neo-adjuvant clinical trials, HRD is shown to be a necessary condition for cisplatin sensitivity. This analysis demonstrates the high performance of the LST genomic signature for HRD detection in breast cancers, which suggests its potential as a biomarker for genetic testing and patient stratification for clinical trials evaluating platinum salts and PARP inhibitors.
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Texto completo:
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Bases de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
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Carcinoma
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Biomarcadores de Tumor
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Reparación del ADN por Recombinación
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Transcriptoma
Límite:
Female
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Humans
Idioma:
En
Revista:
Int J Cancer
Año:
2016
Tipo del documento:
Article
País de afiliación:
Francia