scholarly journals A comprehensive pan-cancer analysis of CD274 gene amplification, tumor mutation burden, microsatellite instability, and PD-L1 expression in Chinese cancer patients

2021 ◽  
Vol 9 (8) ◽  
pp. 677-677
Author(s):  
Guanghui Gao ◽  
Xiao-Dong Zhang ◽  
Hu Qu ◽  
Bing Yao ◽  
Yuxi Zhou ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Cancer Patients ◽  
Gene Amplification ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Chinese Cancer Patients ◽  
Pan Cancer

Exploration of the TMB and hypermutation landscape in Chinese pan-cancer patient by next-generation sequencing.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14575-e14575
Author(s):  
Shuo Wang ◽  
Jiasheng Xu ◽  
Jian Sun ◽  
Deng Wei ◽  
Xinsheng Zhang ◽  
...  
Keyword(s):  
Cancer Patient ◽  
Cancer Patients ◽  
Age And Gender ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Cancer Types ◽  
And Gender ◽  
Chinese Cancer Patients ◽  
Pan Cancer ◽  
Generation Sequencing

e14575 Background: Among a variety of malignant tumors, the level of the patient's TMB was currently an important criterion for clinical judgment whether to adopt immunotherapy. Hypermutation could produce many nearby mutation sites at the same time, which seriously damages genetic material and may cause cancer. Therefore, performing TMB detection on cancer patients and understanding the occurrence of hypermutation in pan-cancer patients will help clinical researchers to further understand the disease characteristics of cancer patients and helped the choice of treatment methods. Previously, TMB and Hypermutation had been tested and studied in pan-cancer patients in the United States and Europe, but rare research was reported in China. In this study, we explored the TMB and hypermutation landscape in Chinese pan-cancer patient by next-generation sequencing. Methods: A total of 8,361 cancer patients from multiple cancer hospitals and research centers in China were included in the study. We sequenced 8,361 Chinese cancer patients from 8 cancer types using the oncopanscan product of Genetron Health Co., Ltd. and calculated the tumor mutation burden of the patients. We separately analyzed the tumor mutation burden of patients in 8 cancer types and analyzed the relationship between the occurrence of hypermutation and the patient's age and gender. Results: The results showed that in pan-cancer, hypermutation patients accounted for 16.97%, and ultrahypermutation patients accounted for 0.78%. Among them, patients with lung cancer have the highest proportion of hypermutation, reaching 27.72%, and patients with colorectal cancer have the highest proportion of ultrahypermutation, reaching 2.86%. Correlation analysis between TMB and age and gender was carried out on 8336 patients. The results showed that in the patients with intrahepatic bile duct cancer, the proportion of men and women was the same. Among the other cancer types, hypermutation patients were more male, and the proportion of men with liver cancer was the largest, with 90 percent. We further explored the correlation between the TMB of pan-cancer patients and the patient’s age, and found that in gastric cancer, liver cancer, and melanoma, the older patients have higher TMB; however, the younger the patients in brain cancer, the higher the TMB ( P<0.05). Conclusions: In this study, we explored the TMB and hypermutation landscape in Chinese pan-Cancer patient for the first time. We found that among Chinese cancer patients, lung cancer patients have the highest proportion of hypermutation. In a variety of cancers, hypermutation patients account for a higher proportion of men, and the older the patient, the higher the TMB.

PD-L1 expression landscape and its relationship with tumor mutation burden in Chinese cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e15267-e15267
Author(s):  
Haihua Yang ◽  
Longgang Cui ◽  
Yuzi Zhang ◽  
Zhengyi Zhao ◽  
Yuezong Bai ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Expression Profiles ◽  
Chinese Patients ◽  
Cancer Type ◽  
Tissue Samples ◽  
Tumor Mutation Burden ◽  
Mutational Burden ◽  
Mutation Burden ◽  
Tumor Mutational Burden ◽  
Chinese Cancer Patients

e15267 Background: Little is known about the pan-cancer PD-L1 expression landscape in Chinese patients although PD-L1 expression has been approved by FDA as a diagnosis for anti-PD-(L)1 therapy in several types of cancer. We did a cross-sectional analysis to assess the PD-L1 expression landscape in Chinese patients and its relationship with Tumor mutation burden (TMB). Methods: Tissue samples were collected from more than 8,000 consecutive cases in China between January, 2017, and August, 2019 and were analyzed by 3D Medicines, a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified laboratory. The method for NGS sequencing and tumor mutational burden (TMB) measurement were described previously. Clinical data and PD-L1 expression profiles were obtained from 8,063 patients whose tissue samples assed quality control. IHC staining for PD-L1 expression was performed using PD-L1 IHC 22C3 pharmDx assay (Dako North America, Carpentaria, CA, U.S.) or Ventana PD-L1 SP263 assay (Ventana Medical Systems, Tucson, AZ, U.S.). PD-L1 expression was determined using Tumor Proportion Score (TPS), the percentage of viable tumor cells stained. Results: PD-L1 expression was examined for 8,063 tissue samples collected from more than 18 different types of solid tumors. There were 4,866 (60%) male and 3,197 (40%) female patients. Their median age was 59 (IQR range, 50-66) years. Given the significance of different cut-points of PD-L1 expression in predicting clinical outcomes, expression levels of PD-L1 were arranged into the following intervals: < 1%, 1%-5%, 5%-50% and ≥50% for each cancer type. Small cell lung cancer (SCLC) had the lowest and Squamous Carcinoma of Head and Neck (HNSC) had the highest levels of PD-L1 expression. Spearman correlation analysis indicated no correlation between PD-L1 and tumor mutational burden (TMB) for Chinese cancer patients (R = 0.1, P < 0.01), which is in line with the previous reports that PD-L1 and TMB were two independent predictors in immunotherapy. Conclusions: The landscape of PD-L1 expression among Chinese cancer population in this study will further assist the utilization of PD-L1 as a predictive biomarker in clinical practice.

scholarly journals Tumor mutation burden in Chinese cancer patients and the underlying driving pathways of high tumor mutation burden across different cancer types

2020 ◽  
Vol 8 (14) ◽  
pp. 860-860
Author(s):  
Xiao-Dong Jiao ◽  
Xiao-Chun Zhang ◽  
Bao-Dong Qin ◽  
Dong Liu ◽  
Liang Liu ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Tumor Mutation Burden ◽  
Mutation Burden ◽  
Cancer Types ◽  
Chinese Cancer Patients

Genomic landscape of FGF/FGFR pathway alternations across 12,372 pan-cancer patients.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13503-e13503
Author(s):  
Yongmei Yin ◽  
Wei Zuo ◽  
He Yan ◽  
Zhengyi Zhao ◽  
Yuzi Zhang ◽  
...  
Keyword(s):  
Growth Factor ◽  
Microsatellite Instability ◽  
Fibroblast Growth Factor ◽  
Cancer Patients ◽  
Growth Factor Receptor ◽  
Great Promise ◽  
Fibroblast Growth ◽  
Tract Cancer ◽  
Chinese Cancer Patients ◽  
Pan Cancer

e13503 Background: The fibroblast growth factor/fibroblast growth factor receptor (FGF/FGFR) signaling pathway is involved in diverse biological processes and plays a crucial role in carcinogenesis. FGFR targeted therapies have shown great promise in the treatment of a multitude of malignancies. This study aimed to assess the alternations of FGF/FGFR pathway and explore the potential relationships between the genetic alternations in a pan-cancer setting. Methods: Next-generation sequencing was conducted with formalin-fixed, paraffin-embedded tumor specimens from 12,372 Chinese cancer patients with over 21 tumor types, including lung cancer (n = 3557), liver cancer (n = 1433), colorectal cancer (n = 1310), biliary tract cancer (n = 960), gastric cancer (n = 758), etc. Somatic mutations including single nucleotide variations (SNVs), amplifications, and fusions were analyzed, and microsatellite instability status was also assayed. Results: Of all patients, the frequency of genomic alterations in FGF/FGFR pathway (FGF3/4/6/10/14/19/23 and FGFR1-4) ranged from 54.1% (86/159) in esophagus cancer, 40.7% (112/275) in bladder/urinary tract cancer, 28.4% (73/257) in head and neck cancer to 5.3% (5/95) in prostate cancer and 4.0% (22/548) in kidney cancer. Amongst all, the highest mutational prevalence fell in FGFR SNV (5.13%) and FGF amplification (5.08%), followed by FGF SNV (3.90%), FGFR amplification (2.89%), FGFR fusion (0.88%), and FGF fusion (0.06%). Partial co-occurrence was observed between alternations of FGFR1 and 11q13 (FGF3/4/19) and between FGF6 and FGF23. On the other side, alternations of FGFR1, FGFR2, FGFR3, and FGFR4 were found to be mutually exclusive ( p< 0.001). In addition, microsatellite instability was found to be positively correlated with FGF/FGFR pathway mutation ( p< 0.001), while was negatively correlated with pathway amplifications ( p= 0.002). Conclusions: Our study investigated the molecular landscape of FGF/FGFR pathway alternations and the interplay between co-occurrence and mutual exclusivity between pathway genes in a large pan-cancer cohort. FGF/FGFR pathway mutations occurs in a variety of solid tumors, indicating that these patients may benefit from FGFR inhibitors.

scholarly journals Noninvasive Detection of Microsatellite Instability and High Tumor Mutation Burden in Cancer Patients Treated with PD-1 Blockade

2019 ◽  
Vol 25 (23) ◽  
pp. 7024-7034 ◽  
Author(s):  
Andrew Georgiadis ◽  
Jennifer N. Durham ◽  
Laurel A. Keefer ◽  
Bjarne R. Bartlett ◽  
Magdalena Zielonka ◽  
...  
Keyword(s):  
Microsatellite Instability ◽  
Cancer Patients ◽  
Noninvasive Detection ◽  
Tumor Mutation Burden ◽  
Mutation Burden

Exploration of the MSI landscape in Chinese pan-cancer patient by Next-Generation Sequencing.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14576-e14576
Author(s):  
Xinlu Liu ◽  
Jiasheng Xu ◽  
Jian Sun ◽  
Deng Wei ◽  
Xinsheng Zhang ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Correlation Analysis ◽  
Cancer Patients ◽  
Cancer Type ◽  
Multiple Tumor ◽  
Treatment Plans ◽  
Cancer Types ◽  
Chinese Cancer Patients ◽  
Colorectal Cancer Patients ◽  
Pan Cancer

e14576 Background: Clinically, MSI had been used as an important molecular marker for the prognosis of colorectal cancer and other solid tumors and the formulation of adjuvant treatment plans, and it had been used to assist in the screening of Lynch syndrome. However, there were currently few reports on the incidence of MSI-H in Chinese pan-cancer patients. This study described the occurrence of MSI in a large multi-center pan-cancer cohort in China, and explored the correlation between MSI and patients' TMB, age, PD-L1 expression and other indicators. Methods: The study included 8361 patients with 8 cancer types from multiple tumor centers. Use immunohistochemistry to detect the expression of MMR protein (MLH1, MSH2, MSH6 and PMS2) in patients with various cancer types to determine the MSI status and detect the expression of PD-L1 in patients. Through NGS technology, 831 genes of 8361 Chinese cancer patients were sequenced and the tumor mutation load of the patients was calculated. The MSI mutations of patients in 8 cancer types were analyzed and the correlation between MSI mutations of patients and the patient's age, TMB and PD-L1 expression was analyzed. Results: The test results showed that MSI patients accounted for 1.66% of pan-cancers. Among them, MSI-H patients accounted for the highest proportion in intestinal cancer, reaching 7.2%. The correlation analysis between MSI and TMB was performed on patients of various cancer types. The results showed that: in each cancer type, MSI-H patients had TMB greater than 10, and 26.83% of MSI-H patients had TMB greater than 100 in colorectal cancer patients. The result of correlation analysis showed that there was no significant correlation between the patient's age and the risk of MSI mutation ( P> 0.05). In addition to PAAD and LUAD, the expression of PD-L1 in MSI-H patients was higher than that in MSS patients in other cancer types( P< 0.05). The correlation analysis between PD-L1 expression and TMB in patients found that in colorectal cancer, the higher the expression of PD-L1, the higher the patient's TMB ( P< 0.05). Conclusions: In this study, we explored the incidence of MSI-H in pan-cancer patients in China and found that the TMB was greater than 10 in patients with MSI-H. Compared with MSS patients, MSI-H patients have higher PD-L1 expression, and the higher the PD-L1 expression in colorectal cancer, the higher the TMB value of patients.

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