scholarly journals MUC4 , MUC16 , and TTN genes mutation correlated with prognosis, and predicted tumor mutation burden and immunotherapy efficacy in gastric cancer and pan‐cancer

2020 ◽  
Vol 10 (4) ◽  
Author(s):  
Yue Yang ◽  
Jieyun Zhang ◽  
Yanxing Chen ◽  
Ruihua Xu ◽  
Qi Zhao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Pan Cancer

Tumor Mutation Burden Computation in Two Pan-Cancer Precision Medicine Next-Generation Sequencing Panels

2020 ◽  
Vol 27 (10) ◽  
pp. 1553-1560 ◽  
Author(s):  
Yongqian Shu ◽  
Xiaohong Wu ◽  
Jia Shen ◽  
Dongdong Luo ◽  
Xiang Li ◽  
...  
Keyword(s):  
Next Generation Sequencing ◽  
Precision Medicine ◽  
Next Generation ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Pan Cancer ◽  
Generation Sequencing

scholarly journals Analysis of Threshold Changes of Tumor Mutation Burden of Gastric Cancer and Its Relationship with Patients’ Prognosis

2021 ◽  
Vol 2021 ◽  
pp. 1-5
Author(s):  
Nan Zhang ◽  
Peiyu Li ◽  
Xin Wu ◽  
Shaoyou Xia ◽  
Xudong Zhao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Pearson Correlation ◽  
Disease Free Survival ◽  
Free Survival ◽  
Tumor Mutation Burden ◽  
D2 Lymph Node Dissection ◽  
Logistic Analysis ◽  
Mutation Burden ◽  
Disease Free

Objective. Gastric cancer is a malignant tumor originating from gastric mucosal epithelium. Here, we aimed to investigate the analysis of the threshold change of gastric cancer tumor mutation burden (TMB) and its relationship with the prognosis of patients. Methods. 256 patients with gastric cancer were selected as subjects. All patients were in the advanced stage and received surgical resection of D2 lymph node dissection. After the operation, a follow-up was performed for 24 months, and the disease-free survival and overall survival of patients were counted. The NGS molecular biological was detected to obtain gastric cancer tumor mutation burden (TMB) data. Pearson correlation analysis software was used to analyze the correlation between TMB threshold and disease-free survival or overall survival of patients with gastric cancer, and the multivariate logistic analysis was performed as well. Results. The disease-free survival period and the overall survival period of patients in the low-to-medium TMB group were both longer than those in the high TMB group. Pearson correlation analysis results showed that the TMB threshold was negatively correlated with the disease-free survival and overall survival of gastric cancer patients. Results from multivariate logistic analysis showed that high TMB thresholds have a greater impact on disease-free survival and overall survival of patients, but the impact of medium and low TMB thresholds on disease-free survival and overall survival of patients is weakened. Conclusions. The TMB threshold level has a predictive effect on the effect of surgical resection of D2 lymph node dissection, and high levels of TMB can significantly affect disease-free survival and overall survival of patients with advanced gastric cancer.

Analysis of mutation detection of POLD1/pole in pan-cancer.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 3142-3142
Author(s):  
Gao Yang ◽  
Jian'An Huang ◽  
Yukun Zu ◽  
Yan Zhang ◽  
Pingping Dai ◽  
...  
Keyword(s):  
Driver Mutation ◽  
Driver Mutations ◽  
Base Substitution ◽  
Tumor Mutation Burden ◽  
Target Capture ◽  
Mutation Burden ◽  
Substitution Mutations ◽  
High Level ◽  
Pan Cancer ◽  
Generation Sequencing

3142 Background: Previous studies proved that mutation of POLD1 and POLE elevates base-substitution mutations and lead to the elevation of tumor mutation burden (TMB). Other signature needs to explore to identify driver mutations in these two genes. Methods: Using gene-panel target-capture next generation sequencing, we analyzed the TMB and POLD1/POLE mutation in 17383 tumor tissue or plasma ctDNA samples from different patients. Results: Tumor mutation burdens were calculated of all the 17383 samples. According to the present research and our panel, we use 10 and 100 Mut/Mb to define hypermutation and ultra-hypermutation. Samples with hypermutation possessed 18.8% (n = 3268) and ultra-hypermutation possessed 0.3% (n = 58). In unselected, hypermutation and ultra-hypermutation group, POLD1 or/and POLE mutations were identified in 3.5% (n = 625), 56.1% (n = 32) and 87.9%(n = 372) samples. There were 0.5% (n = 81), 17.0% (n = 73) and 87.7%(n = 51) identified more than one mutation. These results showed that POLD1 or/and POLE mutations were enriched in samples with high TMB. We screened every known POLE and POLD1 driver mutations. There were 22 ultra-hypermutation samples identified these mutations, including A456P(3), P286R(10), V411L(6), M444K(1), S459F(1) in POLE and R1016H(1) in POLD1. Interestingly, all of them were identified in microsatellite stable (MSS) samples, which suggest that driver mutation may enriched in MSS samples. These already known driver mutation was not detect in 24 high-level microsatellite instability (MSI-H) and ultra-hypermutation samples. We further analyzed 10 POLD1/POLE mutations in other 5 MSS and ultra-hypermutation samples. POLE L424V was a pathogenic germline mutation but not defined as a driver mutation clearly before. POLE P286C had not been biochemically characterized but had different residue with P286R in the same position. Others had not been biochemically characterized (R232H, A234T, V945M, S1064I, Y467H in POLD1, D462N and R749Q, E1956D in POLE). These mutations were potential driver mutations and further research need to be support. Conclusions: We found that not only POLD1 or/and POLE mutations were enriched in samples with high TMB, but also driver mutations were enriched in microsatellite stable tumors. Further researches need to continue to identify more driver mutations of POLD1 and POLE.

scholarly journals Prognostic impact of gene copy number instability and tumor mutation burden in patients with resectable gastric cancer

2020 ◽  
Vol 40 (1) ◽  
pp. 63-66
Author(s):  
Lisheng Cai ◽  
Linhai Li ◽  
Dandan Ren ◽  
Xue Song ◽  
Beibei Mao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Copy Number ◽  
Gene Copy Number ◽  
Gene Copy ◽  
Prognostic Impact ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Resectable Gastric Cancer

scholarly journals Clinicopathological features of tumor mutation burden, Epstein-Barr virus infection, microsatellite instability and PD-L1 status in Chinese patients with gastric cancer

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Li Zhang ◽  
Yinkui Wang ◽  
Zhongwu Li ◽  
Dongmei Lin ◽  
Yiqiang Liu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Microsatellite Instability ◽  
Epstein Barr Virus ◽  
Genetic Alterations ◽  
Chinese Patients ◽  
Epstein Barr Virus Infection ◽  
Tumor Mutation Burden ◽  
Barr Virus ◽  
Mutation Burden ◽  
Epstein Barr

Abstract Objectives Gastric cancer (GC) is the 4th most common type of cancer worldwide. Different GC subtypes have unique molecular features that may have different therapeutic methods. The aim of the present study was to investigate Epstein-Barr virus (EBV) infection, microsatellite instability (MSI) status, the expression of programmed death-ligand 1 (PD-L1) and gene mutations in GC patients. Methods The data of 2504 GC patients, who underwent curative gastrectomy with lymphadenectomy at Peking University Cancer Hospital between 2013 and 2018, were reviewed. We analyzed the clinicopathological factors associated with the immunohistochemistry (IHC) profiles of these patients, and genetic alterations were analyzed using next generation sequencing (NGS). Results Mismatch repair-deficient (d-MMR) GC patients were found to have a higher probability of expressing PD-L1 (p = 0.000, PD-L1 cutoff value = 1%). In addition, 4 and 6.9% of the 2504 gastric cancer patients were EBV-positive and d-MMR, respectively. The number of MLH1/PMS2-negative cases was 126 (6%), and the number of MSH2/MSH6-negative cases was 14 (0.9%). d-MMR status was associated with a intestinal group (p = 0.012), but not with tumor differentiation. Furthermore, MSI and d-MMR GC status (detected by NGS and IHC, respectively) were consistently high, and the rate of MSI was higher in patients with d-MMR GC. A number of genes associated with DNA damage repair were detected in GC patients with MSI, including POLE, ETV6, BRCA and RNF43. In patients with a high tumor mutation burden, the most significantly mutated genes were LRP1B (79.07%), ARID1A (74.42%), RNF43 (69.77%), ZFHX3 (65.12%), TP53 (58.14%), GANS (51.16%), BRCA2 (51.16%), PIK3CA (51.16%), NOTCH1 (51.16%), SMARCA4 (48.84%), ATR (46.51%), POLE (41.86%) and ATM (39.53%). Conclusions Using IHC and NGS, MSI status, protein expression, tumor mutation burden (TMB) and genetic alterations were identified in patients with GC, which provides a theoretical basis for the future clinical treatment of GC.

scholarly journals Clinicopathological features of Epstein-Barr virus infection, microsatellite instability, tumor mutation burden and PD-L1 status in Chinese patients with gastric cancer

2020 ◽  
Author(s):  
Li Zhang ◽  
Aiwen Wu ◽  
Zhongwu Li
Keyword(s):  
Gastric Cancer ◽  
Microsatellite Instability ◽  
Epstein Barr Virus ◽  
Genetic Alterations ◽  
Epstein Barr Virus Infection ◽  
Tumor Mutation Burden ◽  
Barr Virus ◽  
Mutation Burden ◽  
Therapeutic Decisions ◽  
Epstein Barr

Abstract Objectives: Gastric cancer (GC) is the 4th most common type of cancer worldwide. Different GC subtypes exhibit unique molecular features that may potentially guide therapeutic decisions. The aim of the present study was to investigate Epstein-Barr virus (EBV) infection, microsatellite instability (MSI) status, the expression of programmed death-ligand 1 (PD-L1) and gene mutations in patients with surgically-treated GC. Methods: The data of 2,504 GC patients, who underwent potentially curative gastrectomy with lymphadenectomy at Peking University Cancer Hospital between 2013 and 2018, were reviewed from a prospectively collected medical database. We also analyzed the clinicopathological factors associated with the immunohistochemistry (IHC) profiles of these patients, and genetic alterations were analyzed using next generation sequencing (NGS). Results: Mismatch repair-deficient (d-MMR) GC patients were found to have a higher probability of expressing PD-L1 (p<0.001, PD-L1 cutoff value = 1%). In addition, 4 and 6.9% of the 2,504 gastric cancer patients were EBV-positive and d-MMR, respectively. The number of MLH1/PMS2-negative cases was 126 (6%), and the number of MSH2/MSH6-negative cases was 14 (0.9%). d-MMR status was associated with a diffuse/mixed group (p<0.05), but not with tumor differentiation. Furthermore, MSI and d-MMR GC status (detected by NGS and IHC, respectively) were consistently high, and the rate of MSI was higher in patients with d-MMR GC. A number of genes associated with DNA damage repair were detected in GC patients with MSI, including POLE, ETV6, BRCA and RNF43. In patients with a high tumor mutation burden, the most significantly mutated genes were LRP1B (79.07%), ARID1A (74.42%), RNF43 (69.77%), ZFHX3 (65.12%), TP53 (58.14%), GANS (51.16%), BRCA2 (51.16%), PIK3CA (51.16%), NOTCH1 (51.16%), SMARCA4 (48.84%), ATR (46.51%), POLE (41.86%) and ATM (39.53%). Conclusions: Using IHC and NGS, MSI status, protein expression, TMB and genetic alterations were identified in patients with GC, which provides a theoretical basis for the future clinical treatment of GC.

scholarly journals Clinicopathological features of Epstein-Barr virus infection, microsatellite instability, tumor mutation burden and PD-L1 status in Chinese patients with gastric cancer

2020 ◽  
Author(s):  
Li Zhang ◽  
Aiwen Wu ◽  
Zhongwu Li
Keyword(s):  
Gastric Cancer ◽  
Microsatellite Instability ◽  
Epstein Barr Virus ◽  
Genetic Alterations ◽  
Epstein Barr Virus Infection ◽  
Tumor Mutation Burden ◽  
Barr Virus ◽  
Mutation Burden ◽  
Therapeutic Decisions ◽  
Epstein Barr

Abstract Objectives: Gastric cancer (GC) is the 4th most common type of cancer worldwide. Different GC subtypes exhibit unique molecular features that may potentially guide therapeutic decisions. The aim of the present study was to investigate Epstein-Barr virus (EBV) infection, microsatellite instability (MSI) status, the expression of programmed death-ligand 1 (PD-L1) and gene mutations in patients with surgically-treated GC. Methods: The data of 2,504 GC patients, who underwent potentially curative gastrectomy with lymphadenectomy at Peking University Cancer Hospital between 2013 and 2018, were reviewed from a prospectively collected medical database. We also analyzed the clinicopathological factors associated with the immunohistochemistry (IHC) profiles of these patients, and genetic alterations were analyzed using next generation sequencing (NGS). Results: Mismatch repair-deficient (d-MMR) GC patients were found to have a higher probability of expressing PD-L1 (p<0.001, PD-L1 cutoff value = 1%). In addition, 4 and 6.9% of the 2,504 gastric cancer patients were EBV-positive and d-MMR, respectively. The number of MLH1/PMS2-negative cases was 126 (6%), and the number of MSH2/MSH6-negative cases was 14 (0.9%). d-MMR status was associated with a diffuse/mixed group (p<0.05), but not with tumor differentiation. Furthermore, MSI and d-MMR GC status (detected by NGS and IHC, respectively) were consistently high, and the rate of MSI was higher in patients with d-MMR GC. A number of genes associated with DNA damage repair were detected in GC patients with MSI, including POLE, ETV6, BRCA and RNF43. In patients with a high tumor mutation burden, the most significantly mutated genes were LRP1B (79.07%), ARID1A (74.42%), RNF43 (69.77%), ZFHX3 (65.12%), TP53 (58.14%), GANS (51.16%), BRCA2 (51.16%), PIK3CA (51.16%), NOTCH1 (51.16%), SMARCA4 (48.84%), ATR (46.51%), POLE (41.86%) and ATM (39.53%). Conclusions: Using IHC and NGS, MSI status, protein expression, TMB and genetic alterations were identified in patients with GC, which provides a theoretical basis for the future clinical treatment of GC.

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