Skip to main content
main-content

21.08.2018 | Original Article

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

Zeitschrift:
Gastric Cancer
Autoren:
Han Hong Lee, Su Young Kim, Eun Sun Jung, Jinseon Yoo, Tae-Min Kim
Wichtige Hinweise

Electronic supplementary material

The online version of this article (https://​doi.​org/​10.​1007/​s10120-018-0870-6) contains supplementary material, which is available to authorized users.

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.

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

★ PREMIUM-INHALT
e.Med Interdisziplinär

Mit e.Med Interdisziplinär erhalten Sie Zugang zu allen CME-Fortbildungen und Fachzeitschriften auf SpringerMedizin.de. Zusätzlich können Sie eine Zeitschrift Ihrer Wahl in gedruckter Form beziehen – ohne Aufpreis.

Bis zum 22.10. bestellen und 100 € sparen!

Weitere Produktempfehlungen anzeigen
Zusatzmaterial
Supplementary material 1 (PDF 424 KB)
10120_2018_870_MOESM1_ESM.pdf
Supplementary material 2 (XLSX 11 KB)
10120_2018_870_MOESM2_ESM.xlsx
Supplementary material 3 (XLSX 1015 KB)
10120_2018_870_MOESM3_ESM.xlsx
Literatur
Über diesen Artikel
  1. Das kostenlose Testabonnement läuft nach 14 Tagen automatisch und formlos aus. Dieses Abonnement kann nur einmal getestet werden.

  2. Das kostenlose Testabonnement läuft nach 14 Tagen automatisch und formlos aus. Dieses Abonnement kann nur einmal getestet werden.

Neu im Fachgebiet Chirurgie

 

 

 
 

Mail Icon II Newsletter

Bestellen Sie unseren kostenlosen Newsletter Update Chirurgie und bleiben Sie gut informiert – ganz bequem per eMail.

Bildnachweise