Clonality analysis of synchronous gastro-oesophageal junction carcinoma and distal gastric cancer by whole-exome sequencing

Xiaofang Xing, Shuqin Jia, Jianmin Wu, Qin Feng, Bin Dong, Bo Li, Yongning Jia, Fei Shan, Ying'ai Li, Yan Zhang, Ying Hu, Xiaodong Wang, Xiangtao Liu, Weishi Yu, Lianhai Zhang, Zhaode Bu, Aiwen Wu, Ziyu Li, Jiafu Ji

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Abstract

Gastro-oesophageal junction (GEJ) carcinoma and distal gastric cancer (GC) have distinct epidemiology and clinical features and their relationship is uncertain. Synchronous multiple gastric cancers located mostly at proximal and distal sites provide rare specimens for investigating the comprehensive genomic relationships among these cancers in the context of identical genetic circumstances. Formalin-fixed, paraffin-embedded (FFPE) samples from 12 patients with synchronous GEJ carcinoma and distal GC were collected in this study. Whole-exome sequencing (WES) was performed using normal tissues as a control. Mutational profiling, clonality analysis, a detailed clinico-pathological review, determination of MSI status, EBER in situ hybridization (ISH), and programmed cell death 1 (PD-1)/programmed death-ligand 1 (PD-L1) immunohistochemical staining were performed. Twenty-three of the 24 samples were microsatellite-stable (MSS). Subclonal analysis revealed that nine pairs of GEJ and distal GC tumours in neoadjuvant chemotherapy naïve patients developed independently from different origins. Two patients who received neoadjuvant chemotherapy shared clonal origins with highly similar somatic alterations. The remaining one patient who shared a rare mutation died within 6.2 months at the N3 stage. However, the enriched pathway identified from the overall mutation spectra in distal GC and GEJ carcinoma showed the close relationship of these cancers. Thus, although these cancers may have similar characteristics, histopathological and genetic profiling from single tumour specimens may still underestimate the mutational burden and somatic heterogeneity of multiple GCs. In addition, this series of cases also showed a PD-L1 expression rate of 58.3% and 66.7% in distal GC and GEJ carcinoma, respectively, with all the cases expressing PD-1. This result suggests the potential benefit of immunotherapeutic treatments.

Original languageEnglish (US)
Pages (from-to)165-175
Number of pages11
JournalJournal of Pathology
Volume243
Issue number2
DOIs
StatePublished - Oct 1 2017

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Exome
Stomach Neoplasms
Carcinoma
Neoplasms
CD274 Antigen
Drug Therapy
Mutation
Paraffin
Microsatellite Repeats
Formaldehyde
In Situ Hybridization
Epidemiology
Cell Death
Staining and Labeling
Ligands

Keywords

  • clonality
  • gastric cancer
  • gastro-oesophageal junction carcinoma
  • synchronous
  • whole-exome sequencing

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Clonality analysis of synchronous gastro-oesophageal junction carcinoma and distal gastric cancer by whole-exome sequencing. / Xing, Xiaofang; Jia, Shuqin; Wu, Jianmin; Feng, Qin; Dong, Bin; Li, Bo; Jia, Yongning; Shan, Fei; Li, Ying'ai; Zhang, Yan; Hu, Ying; Wang, Xiaodong; Liu, Xiangtao; Yu, Weishi; Zhang, Lianhai; Bu, Zhaode; Wu, Aiwen; Li, Ziyu; Ji, Jiafu.

In: Journal of Pathology, Vol. 243, No. 2, 01.10.2017, p. 165-175.

Research output: Contribution to journalArticle

Xing, X, Jia, S, Wu, J, Feng, Q, Dong, B, Li, B, Jia, Y, Shan, F, Li, Y, Zhang, Y, Hu, Y, Wang, X, Liu, X, Yu, W, Zhang, L, Bu, Z, Wu, A, Li, Z & Ji, J 2017, 'Clonality analysis of synchronous gastro-oesophageal junction carcinoma and distal gastric cancer by whole-exome sequencing', Journal of Pathology, vol. 243, no. 2, pp. 165-175. https://doi.org/10.1002/path.4932
Xing, Xiaofang ; Jia, Shuqin ; Wu, Jianmin ; Feng, Qin ; Dong, Bin ; Li, Bo ; Jia, Yongning ; Shan, Fei ; Li, Ying'ai ; Zhang, Yan ; Hu, Ying ; Wang, Xiaodong ; Liu, Xiangtao ; Yu, Weishi ; Zhang, Lianhai ; Bu, Zhaode ; Wu, Aiwen ; Li, Ziyu ; Ji, Jiafu. / Clonality analysis of synchronous gastro-oesophageal junction carcinoma and distal gastric cancer by whole-exome sequencing. In: Journal of Pathology. 2017 ; Vol. 243, No. 2. pp. 165-175.
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AU - Dong, Bin

AU - Li, Bo

AU - Jia, Yongning

AU - Shan, Fei

AU - Li, Ying'ai

AU - Zhang, Yan

AU - Hu, Ying

AU - Wang, Xiaodong

AU - Liu, Xiangtao

AU - Yu, Weishi

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AU - Ji, Jiafu

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