Oncotarget

Research Papers:

Whole-exome sequencing to identify somatic mutations in peritoneal metastatic gastric adenocarcinoma: A preliminary study

Hao Liu _, Fengping Li, Yu Zhu, Tingting Li, Haipeng Huang, Tian Lin, Yanfeng Hu, Xiaolong Qi, Jiang Yu and Guoxin Li

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Oncotarget. 2016; 7:43894-43906. https://doi.org/10.18632/oncotarget.9707

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Abstract

Hao Liu1,*, Fengping Li1,*, Yu Zhu1, Tingting Li1, Haipeng Huang1, Tian Lin1, Yanfeng Hu1, Xiaolong Qi1, Jiang Yu1, Guoxin Li1

1Department of General Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China

*These authors contributed equally to this work and should be considered co-first authors

Correspondence to:

Guoxin Li, email: gzliguoxin@163.com

Jiang Yu, email: balbc@163.com

Keywords: gastric cancer, peritoneal metastasis, whole-exome sequencing (WES), Sanger sequencing, somatic mutation

Received: February 21, 2016     Accepted: May 16, 2016     Published: May 30, 2016

ABSTRACT

Peritoneal metastasis occurs in more than half of patients with unresectable or recurrent gastric cancer and is associated with the worst prognosis. The associated genomic events and pathogenesis remain ambiguous. The aim of the present study was to characterize the mutation spectrum of gastric cancer with peritoneal metastasis and provide a basis for the identification of new biomarkers and treatment targets. Matched pairs of normal gastric mucosa and peritoneal tissue and matched pairs of primary tumor and peritoneal metastasis were collected from one patient for whole-exome sequencing (WES); Sanger sequencing was employed to confirm the somatic mutations. G>A and C>T mutations were the two most frequent transversions among the somatic mutations. We confirmed 48somatic mutations in the primary site and 49 in the peritoneal site. Additionally, 25 non-synonymous somatic variations (single-nucleotide variants, SNVs) and 2 somatic insertions/deletions (INDELs) were confirmed in the primary tumor, and 30 SNVs and 5 INDELs were verified in the peritoneal metastasis. Approximately 59% of the somatic mutations were shared between the primary and metastatic site. Five genes (TP53, BAI1, THSD1, ARID2, and KIAA2022) verified in our study were also mutated at a frequency greater than 5%in the COSMIC database. We also identified 9genes (ERBB4, ZNF721, NT5E, PDE10A, CA1, NUMB, NBN, ZFYVE16, and NCAM1) that were only mutated in metastasis and are expected to become treatment targets. In conclusion, we observed that the majority of the somatic mutations in the primary site persisted in metastasis, whereas several single-nucleotide polymorphisms occurred de novo at the second site.


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