Allele-specific genomic data elucidate the role of somatic gain and copy-number neutral loss of heterozygosity in cancer.
Cell Syst
; 13(2): 183-193.e7, 2022 02 16.
Article
en En
| MEDLINE
| ID: mdl-34731645
ABSTRACT
Pan-cancer studies sketched the genomic landscape of the tumor types spectrum. We delineated the purity- and ploidy-adjusted allele-specific profiles of 4,950 patients across 27 tumor types from the Cancer Genome Atlas (TCGA). Leveraging allele-specific data, we reclassified as loss of heterozygosity (LOH) 9% and 7% of apparent copy-number wild-type and gain calls, respectively, and overall observed more than 18 million allelic imbalance somatic events at the gene level. Reclassification of copy-number events revealed associations between driver mutations and LOH, pointing out the timings between the occurrence of point mutations and copy-number events. Integrating allele-specific genomics and matched transcriptomics, we observed that allele-specific gene status is relevant in the regulation of TP53 and its targets. Further, we disclosed the role of copy-neutral LOH in the impairment of tumor suppressor genes and in disease progression. Our results highlight the role of LOH in cancer and contribute to the understanding of tumor progression.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Pérdida de Heterocigocidad
/
Neoplasias
Límite:
Humans
Idioma:
En
Revista:
Cell Syst
Año:
2022
Tipo del documento:
Article
País de afiliación:
Italia