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Erschienen in: Gastric Cancer 2/2019

01.03.2019 | Original Article

Mutation heterogeneity between primary gastric cancers and their matched lymph node metastases

verfasst von: Han Hong Lee, Su Young Kim, Eun Sun Jung, Jinseon Yoo, Tae-Min Kim

Erschienen in: Gastric Cancer | Ausgabe 2/2019

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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.
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Metadaten
Titel
Mutation heterogeneity between primary gastric cancers and their matched lymph node metastases
verfasst von
Han Hong Lee
Su Young Kim
Eun Sun Jung
Jinseon Yoo
Tae-Min Kim
Publikationsdatum
01.03.2019
Verlag
Springer Singapore
Erschienen in
Gastric Cancer / Ausgabe 2/2019
Print ISSN: 1436-3291
Elektronische ISSN: 1436-3305
DOI
https://doi.org/10.1007/s10120-018-0870-6

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