Abstract 4803
Background
Hereditary diffuse gastric cancer (HDGC) is closely related to germline mutation of CDH1. In addition, potential pathogenic germline variants in other candidate genes were detected in FGC and HDGC families. However, comprehensive genetic profile of HDGC predisposing gene variants in Chinese Familial gastric cancer (FGC) and HDGC patients are yet to be elucidated.
Methods
We collected peripheral blood from 28 early-onset DGC patients and from a first degree relative DGC patient who was diagnosed at age of 50. All 29 patients fulfilled IGCLC 2015 criteria for HDGC clinical diagnosis and genetic testing. Genomic DNA was extracted from peripheral blood followed by Whole Exome Sequencing (WES) with average sequencing depth of at least 100X. Gastric ancer predisposing SNV and Indel candidates were filtered based on population allele frequencies in public nucleotide polymorphism databases and corresponding functional impact was predicted by in silico tools.
Results
Among previously reported gastric cancer susceptibility genes, CDH1, BRCA2, MAP3K6 expressed the most predisposing SNV and Indel candidates. In addition, a novel splice-site variant, c.2165-1G>A, in CDH1 was detected in a Chinese early-onset HDGC patient who developed ovarian metastasis. Moreover, BCR gene exhibited as the most prevalent gastric cancer predisposing gene with filtered variants primarily enriched in RhoGAP domain. Pathway enrichment analysis showed that the top three predisposing variant candidates were enriched in the following signalling pathway: ECM-receptor interaction (P-Value: 0.001), focal adhesion (P-Value: 0.02) and protein digestion and absorption (P-Value: 0.002).
Conclusions
This study suggested that CDH1, BRCA2, MAP3K6 may act as potential gastric cancer susceptibility genes in Chinese early-onset HDGC patients. Further study may be required to investigate the functional role of BCR abnormality, especially in its RhoGAP domain, in the tumorigenesis of gastric cancer. Moreover, to further investigate molecular mechanisms of early-onset gastric cancer, one may consider genes involved in three signalling pathways: ECM-receptor interaction, focal adhesion and protein digestion and absorption.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Peking University Cancer Hospital.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Resources from the same session
3773 - Impact of centralisation of national cancer services on patient outcomes for hepatobiliary cancers in Ireland 2000 – 2016
Presenter: David O Reilly
Session: Poster Display session 2
Resources:
Abstract
3180 - Genomic analysis of hepatobiliary lithiasis associated cholangiocarcinoma revealed a distinct subtype feature.
Presenter: Lunda Gu
Session: Poster Display session 2
Resources:
Abstract
4891 - Comparison of the impact of stereotactic body radiation therapy vs. radiofrequency ablation on liver function in patients with single hepatocellular carcinoma: A propensity score matching analysis
Presenter: Masayuki Ueno
Session: Poster Display session 2
Resources:
Abstract
3203 - Exploratory analysis based on tumor location and early metabolic tumor response of REACHIN, a randomized double-blinded placebo-controlled phase II trial of regorafenib after failure of gemcitabine/platinum-based chemotherapy for advanced and metastatic biliary tract tumors.
Presenter: Anne Demols
Session: Poster Display session 2
Resources:
Abstract
1602 - Predictive Value of Neutrophil-Lymphocyte Ratio (NLR) And Platelet-Lymphocyte Ratio (PLR) In Hepatocellular Carcinoma (HCC) Patients Treated with Nivolumab (N)
Presenter: Sirish Dharmapuri
Session: Poster Display session 2
Resources:
Abstract
2848 - Preliminary Safety and Pharmacokinetics of a New Lysosomotropic Oral Agent, GNS561, in a First-in-Human Study in Advanced Primary Liver Cancer Patients
Presenter: Ahmad Awada
Session: Poster Display session 2
Resources:
Abstract
1396 - A phase 1b trial of lenvatinib (LEN) plus pembrolizumab (PEMBRO) in unresectable hepatocellular carcinoma (uHCC): updated results
Presenter: Josep Llovet
Session: Poster Display session 2
Resources:
Abstract
1139 - Multicentric prospective study of validation of angiogenesis-related gene polymorphisms in HCC patients treated with sorafenib: Final results of INNOVATE study
Presenter: Andrea Casadei-gardini
Session: Poster Display session 2
Resources:
Abstract
4688 - Prognostic and predictive factors from the phase 3 CELESTIAL trial of cabozantinib (C) versus placebo (P) in previously treated advanced hepatocellular carcinoma (aHCC)
Presenter: Tim Meyer
Session: Poster Display session 2
Resources:
Abstract
1492 - A phase Ib study of pembrolizumab following trans-arterial chemoembolization (TACE) in hepatocellular carcinoma (HCC): PETAL.
Presenter: David Pinato
Session: Poster Display session 2
Resources:
Abstract