Computational identification of mutator-derived lncRNA signatures of genome instability for improving the clinical outcome of cancers: a case study in breast cancer.
Brief Bioinform
; 21(5): 1742-1755, 2020 09 25.
Article
en En
| MEDLINE
| ID: mdl-31665214
ABSTRACT
Emerging evidence revealed the critical roles of long non-coding RNAs (lncRNAs) in maintaining genomic instability. However, identification of genome instability-associated lncRNAs and their clinical significance in cancers remain largely unexplored. Here, we developed a mutator hypothesis-derived computational frame combining lncRNA expression profiles and somatic mutation profiles in a tumor genome and identified 128 novel genomic instability-associated lncRNAs in breast cancer as a case study. We then identified a genome instability-derived two lncRNA-based gene signature (GILncSig) that stratified patients into high- and low-risk groups with significantly different outcome and was further validated in multiple independent patient cohorts. Furthermore, the GILncSig correlated with genomic mutation rate in both ovarian cancer and breast cancer, indicating its potential as a measurement of the degree of genome instability. The GILncSig was able to divide TP53 wide-type patients into two risk groups, with the low-risk group showing significantly improved outcome and the high-risk group showing no significant difference compared with those with TP53 mutation. In summary, this study provided a critical approach and resource for further studies examining the role of lncRNAs in genome instability and introduced a potential new avenue for identifying genomic instability-associated cancer biomarkers.
Palabras clave
Texto completo:
1
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Inestabilidad Genómica
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ARN Largo no Codificante
/
Mutación
Tipo de estudio:
Diagnostic_studies
Límite:
Female
/
Humans
Idioma:
En
Revista:
Brief Bioinform
Asunto de la revista:
BIOLOGIA
/
INFORMATICA MEDICA
Año:
2020
Tipo del documento:
Article