Mutation heterogeneity between primary gastric cancers and their matched lymph node metastases.
Gastric Cancer
; 22(2): 323-334, 2019 03.
Article
em En
| MEDLINE
| ID: mdl-30132154
ABSTRACT
BACKGROUND:
The acquisition of an invasive phenotype by a tumor cell is a crucial step of malignant transformation. The underlying genetic mechanisms in gastric cancer (GC) are not well understood.METHODS:
We performed whole-exome sequencing of 15 pairs of primary GC and their matched lymph node (LN) metastases (10 primary GCs with single matched LNs and 5 primary GCs with three LNs per case, respectively). Somatic alterations including single nucleotide variations, short insertions/deletions including locus-level microsatellite instability and copy number alterations were identified and compared between the primary and metastatic LN genomes.RESULTS:
Mutation abundance was comparable between the primary GC and LN metastases, but the extent of mutation overlap or the mutation heterogeneity between primary and LN genomes varied substantially. Primary- or LN-specific mutations could be distinguished from common mutations in terms of mutation spectra and functional categories, suggesting that the mutation forces are not constant during gastric carcinogenesis. A spatial distribution revealed TP53 mutations as common mutations along with a number of region-specific mutations, such as primary-specific SMARCA4 and LN-specific CTNNB1 mutations. The subclonal architectures of common mutations were largely conserved between primary GC and LN metastatic genomes. The mutation-based phylogenetic analyses further showed that LN metastases may have arisen from homogeneous subclones of primary tumors.CONCLUSIONS:
The abundance and spatial distribution of mutations may provide clues on the evolutionary relationship between primary and matched LN genomes. Gene-level analyses further distinguished the early addicted cancer drivers such as TP53 mutations from late acquired region-specific mutations.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Neoplasias Gástricas
/
Metástase Linfática
Limite:
Aged
/
Aged80
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Gastric Cancer
Assunto da revista:
GASTROENTEROLOGIA
/
NEOPLASIAS
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Coréia do Sul