Precise microdissection of gastric mixed adeno-neuroendocrine carcinoma dissects its genomic landscape and evolutionary clonal origins.
Cell Rep
; 42(6): 112576, 2023 06 27.
Article
em En
| MEDLINE
| ID: mdl-37285266
ABSTRACT
Gastric mixed adenoneuroendocrine carcinoma (MANEC) is a clinically aggressive and heterogeneous tumor composed of adenocarcinoma (ACA) and neuroendocrine carcinoma (NEC). The genomic properties and evolutionary clonal origins of MANEC remain unclear. We conduct whole-exome and multiregional sequencing on 101 samples from 33 patients to elucidate their evolutionary paths. We identify four significantly mutated genes, TP53, RB1, APC, and CTNNB1. MANEC resembles chromosomal instability stomach adenocarcinoma in that whole-genome doubling in MANEC is predominant and occurs earlier than most copy-number losses. All tumors are of monoclonal origin, and NEC components show more aggressive genomic properties than their ACA counterparts. The phylogenetic trees show two tumor divergence patterns, including sequential and parallel divergence. Furthermore, ACA-to-NEC rather than NEC-to-ACA transition is confirmed by immunohistochemistry on 6 biomarkers in ACA- and NEC-dominant regions. These results provide insights into the clonal origin and tumor differentiation of MANEC.
Palavras-chave
CP: Cancer; CP: Genomics; evolutionary clonal origins; gastric mixed adenoneuroendocrine carcinoma; mixed neuroendocrine tumors; mixed neuroendocrine-nonneuroendocrine neoplasm; multi-regional sequencing; parallel divergence; phylogenetic construction; tumor differentiation; tumor evolution; whole-genome doubling
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
/
Adenocarcinoma
/
Carcinoma Neuroendócrino
Limite:
Humans
Idioma:
En
Ano de publicação:
2023
Tipo de documento:
Article