Detection of genes related to peritoneal metastasis of primary gastric cancer based on large-panel Next Generation Sequencing.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e16026-e16026
Author(s):  
Si Tao ◽  
Xin Liu ◽  
Chunhui Jin ◽  
Rongrong Chen

e16026 Background: Peritoneum is a common site of recurrence and metastasis of gastric cancer. The traditional clinical methods have poor sensitivity for the diagnosis of peritoneal metastasis, and there is no effective marker for predicting peritoneal metastasis of gastric cancer. In this study, the genetic profiles of primary tumors in gastric cancer patients with and without peritoneal metastasis, as well as the genetic alterations before and after metastasis in the same patient were analyzed to explore the genetic alterations associated with peritoneal metastasis. Methods: 232 patients with stage Ⅳ gastric cancer were divided into PM group and non-PM group according to whether there was peritoneal metastasis, DNA based Next Generation Sequencing (NGS) with a 1021 gene panel was performed on their samples. Clinical information was obtained synchronously from physicians and surgeons. Results: There was no significant difference in baseline clinical characteristics between patients in PM and non-PM groups. Molecular analysis revealed that in the PM group, the incidence of CDH1, CDH23, HDAC1, IDH1, KRAS, MED12, RHOA, NOTCH2, TGFBR1 mutations was significantly higher in PM group than that in non-PM group, and these mutated genes were mostly located in wnt/β- catenin and MAPK signaling pathway. On the contrary, the incidence of ERBB2 and CCNE1 amplification was significantly higher in non-PM group than in the other group. Further analysis of samples before and after peritoneal metastasis of 13 patients did not find significant differences in genetic alterations. Conclusions: Compared with other sites, the primary tumor of gastric cancer patients with peritoneal metastasis seems to have its unique molecular characteristics, and large-panel NGS can help us identify this part of patients. Future research may need to clarify whether more radical treatment strategies are needed for these patients.

2020 ◽  
Author(s):  
Li Zhang ◽  
Aiwen Wu ◽  
Zhongwu Li

Abstract Objectives: Gastric cancer is the 4th most common cancer worldwide. Different subtype showed unique molecular features that could potentially guide therapeutic decisions. The aim of this study was to investigate the Epstein-Barr virus infection, microsatellite instability status, PD-L1 expression and gene mutation in surgically treated gastric cancer patients. Methods: We reviewed all GC patients who underwent potentially curative gastroectomy with lymphadenectomy at Peking University Cancer Hospital between 2013 and 2018 from a prospective collected medical database. We analyzed the clinic-pathological factors associated with immunohistochemistry profiles. We also analyzed gene changes through next-generation sequencing. Results: d-MMR gastric cancer patients are more likely to expression programmed death-ligand 1 (p<0.001, programmed death-ligand 1 cut off value 1%). EBV-positive and d-MMR patients were identified in 4% and 7.5% of the 2504 gastric cancer patients, respectively. The MLH1/PMS2 negative case number was 126. The MSH2/MSH6 negative case number was 14. d-MMR status was related to diffuse/mixed group (p<0.05), but not related to tumor differentiation. In our study, the microsatellite instability results detected by next generation sequencing and d-MMR gastric cancer results detected by immunohistochemistry were in high consistency. d-MMR gastric cancer patients had more microsatellite instability core. Many pathogenic genes were detected in microsatellite instability gastric cancer patients, such as POLE, ETV6, TP53, BRCA, RNF43 and other genes. Conclusion: Through immunohistochemistry and next generation sequencing, we got MSI status, protein expression, TMB and gene changes of GC, which provided a theoretical basis for future G clinical treatment.


2016 ◽  
Vol 39 (2) ◽  
pp. 189-198 ◽  
Author(s):  
Antonette El-Husny ◽  
Milene Raiol-Moraes ◽  
Marcos Amador ◽  
André M. Ribeiro-dos-Santos ◽  
André Montagnini ◽  
...  

2020 ◽  
Vol 74 (1) ◽  
pp. 19-24 ◽  
Author(s):  
Malene Nielsen ◽  
Martin Graversen ◽  
Signe Bremholm Ellebæk ◽  
Thomas Kielsgaard Kristensen ◽  
Claus Fristrup ◽  
...  

BackgroundPeritoneal metastasis from pancreatic cancer (PM-PC) may be treated with repeated pressurised intraperitoneal aerosol chemotherapy (PIPAC). Utility of next-generation sequencing (NGS) to detect cancer-related mutations in peritoneal quadrant biopsies (QBs) and peritoneal fluid (PF) after systemic and PIPAC treatment has not been evaluated. Around 90% of pancreatic cancers (PCs) harbour a KRAS mutation, making PC ideal for the evaluation of this aspect.AimsEvaluation of PM-PC in terms of (1) histological response to PIPAC using Peritoneal Regression Grading Score (PRGS), (2) clinical characteristics and (3) frequency of mutations in QBs and PF before and after PIPAC.MethodsPeritoneal QBs and PF were obtained prior to each PIPAC. NGS for 22 cancer-related genes was performed on primary tumours, QBs and PFs. Response was assessed by the four-tiered PRGS.ResultsSixteen patients treated with a median of three PIPAC procedures were included. The mean PRGS was reduced from 1.91 to 1.58 (p=0.02). Fifty-seven specimens (13 primary tumours, 2 metastatic lymph nodes, 16 PFs and 26 QB sets) were analysed with NGS. KRAS mutation was found in 14/16 patients (87.50%) and in QBs, primary tumours and PF in 8/12 (66.67%), 8/13 (61.53%) and 6/9 (66.67%). The median overall survival was 9.9 months (SE 1.5, 95% CI 4.9 to 13.9).ConclusionPIPAC induces histological response in the majority of patients with PM-PC. KRAS mutation can be found in PM-PC after PIPAC at a frequency similar to the primaries. NGS may be used to detect predictive mutations in PM-PC of various origins, also when only post-PIPAC QBs or PFs are available.


2019 ◽  
Vol 02 (03) ◽  
pp. 105-118
Author(s):  
Hui Cai ◽  
Xiaomei Hou ◽  
Yibo Ding ◽  
Zhongxing Fu ◽  
Ling Wang ◽  
...  

Gastric cancer (GC) is one of the most commonly diagnosed malignancies worldwide, and is caused by complex interactions of multiple risk factors such as environmental (Helicobacter pylori and Epstein–Barr Virus), hereditary (genetic alterations and epigenetic modifications), as well as dietary and lifestyle factors. GC is usually detected at an advanced stage, with a dismal prognosis. Even for patients with similar clinical or pathologic stage receiving similar treatment, the outcomes are still uneven and unpredictable. To better incorporate genetic and epigenetic profiles into GC prognostic predication, gene expression signatures have been developed to predict GC outcomes. More recently, the advancement of high-throughput sequencing technology, also known as next-generation sequencing (NGS) technology, and analysis has provided the basis for accurate molecular classification of GC tumors. Here, we summarized and updated the literature related to NGS studies of GC, including whole-genome sequencing, whole-exome sequencing, RNA sequencing, and targeted sequencing, and discussed current progresses. NGS has facilitated the identification of genetic/epigenetic targets for screening as well as development of targeted agent therapy, thus enabling individualized patient management and treatment.


Gene ◽  
2020 ◽  
Vol 726 ◽  
pp. 144176 ◽  
Author(s):  
Xuefeng Bu ◽  
Xuanfeng Zhang ◽  
Wenkang Luan ◽  
Riting Zhang ◽  
Yao Zhang ◽  
...  

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