A DNA-mutational panel for liquid biopsy-based pan-cancer early detection.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13687-e13687
Author(s):  
Zhao Yi ◽  
Weizhi Chen ◽  
Ji He
Keyword(s):  
Early Detection ◽  
Cancer Patients ◽  
Liquid Biopsy ◽  
Somatic Mutations ◽  
Asian Population ◽  
Plasma Samples ◽  
Sequencing Data ◽  
Cancer Early Detection ◽  
Chinese Cancer Patients ◽  
Pan Cancer

e13687 Background: Early detection through liquid biopsy can significantly increase the successful chances of treatment. The sensitivity and specificity of early detection are limited by lower signal-to-noise ratio. Thus, well design of liquid biopsy panel is important. Methods: We adopted comprehensive data sources for designing the liquid biopsy panel, including databases of TCGA, ICGC, COSMIC, MSK Cancer Hotspots, while the panel of HCCscreen and CancerSeek. We also considered the database of somatic mutations in Chinese cancer patients generated by us (Genecast (Beijing) Biotechnology Co., Ltd.). We first calculated pan-cancer carrier ratio of somatic mutations in each database and constructed the distribution of mutation counts on step-wise increased carrier ratio. Then, we selected the set of somatic mutations with “elbow point” carrier ratio from each database as part of the panel. Finally, we integrated collected hotspots with the panel of HCCscreen and CancerSeek. Results: We selected 408, 521, 214, 146 and 330 hotspots from databases of TCGA, ICGC, COSMIC, MSK Cancer Hotspots and somatic mutations in Chinese cancer patients, respectively. After integration with the panel of HCCscreen and CancerSeek, this designed panel contains 3,334 bases distributed on 23 chromosomes and 915 gene models. Comparison of hotspots collected from different databases showed that few of them shared the same genomic location except for ones from the database of MSK Cancer Hotspots, indicating the well complementarity between them. Especially, there are 186 unique hotspots collected from the database of somatic mutations in Chinese cancer patients, which can improve the sensitivity of early detection for Chinese and Asian population. Next, we evaluated detected sensitivity of the designed panel based on sequencing data of plasma samples from more than 12,000 Chinese cancer patients collected in Genecast. The result showed that the maximum sensitivity is 66.67% for small cell lung cancer and the overall sensitivity is 45.71% for 26 cancer types, in which hotspots uniquely collected from the database of somatic mutations in Chinese cancer patients accounted for 5.11%. Conclusions: We designed a liquid biopsy panel for pan-cancer early detection and evaluated its sensitivity based on sequencing data of plasma samples from more than 12,000 Chinese cancer patients. Satisfactory performance of our designed panel shows its potential application in cancer screening for healthy and highly risky individuals.

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.

scholarly journals Delivering on the promise of early detection with liquid biopsies

2022 ◽  
Author(s):  
David Crosby
Keyword(s):  
Cancer Research ◽  
Cancer Therapy ◽  
Early Detection ◽  
Liquid Biopsy ◽  
Therapy Monitoring ◽  
Disease Relapse ◽  
Liquid Biopsies ◽  
Cancer Early Detection ◽  
Ideal Position

AbstractLiquid biopsy approaches are relatively well developed for cancer therapy monitoring and disease relapse, but they also have incredible potential in the cancer early detection and screening field. There are, however, several challenges to overcome before this potential can be met. Research in this area needs to be cohesive and, as a driver of research, Cancer Research UK is in an ideal position to enable this.

scholarly journals A comprehensive pan-cancer study of FGFR aberrations in Chinese cancer patients

2019 ◽  
Vol 30 ◽  
pp. v44
Author(s):  
Y. Gao ◽  
W. Zhu ◽  
Q. He ◽  
Y. Liu ◽  
X. Chen ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Cancer Study ◽  
Chinese Cancer Patients ◽  
Pan Cancer

The prevalence of CDK12 alterations in Chinese cancer patients and the association with tumor mutation burden(TMB) and survival.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13663-e13663
Author(s):  
Ke Li ◽  
Xi Guo ◽  
Yunhua Mao ◽  
Mengmei Yang ◽  
Mengli Huang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Molecular Subtype ◽  
Prostate Adenocarcinoma ◽  
Chinese Patients ◽  
Cyclin Dependent Kinase ◽  
Poor Prognostic Factor ◽  
Cancer Types ◽  
Chinese Cancer Patients ◽  
Pan Cancer

e13663 Background: Cyclin-dependent kinase 12 (CDK12) is a cyclin-dependent kinase that regulates transcription and RNA splicing, thereby modulating multiple cellular processes. It has been suggested that CDK12 loss-of-function mutations lead to a higher neoantigen burden and favorable responses to PD-1 inhibitors in advanced prostate cancer. Given this potentially actionable molecular subtype, we sought to determine the prevalence of CDK12 alterations in Chinese cancer patients and the association with TMB and overall survival(OS). Methods: The prevalence of CDK12 alterations were queried in 3D Medicines database with 15,745 Chinese cancer patients involved. Whole-exome sequencing data of 464 patients with prostate adenocarcinoma(PRAD) from the Cancer Genome Altas (TCGA) were downloaded to explore the association between CDK12 gene alteration and OS. And the association with TMB were analyzed in a cohort of 731 patients with various cancer types published by Memorial Sloan Kettering (MSKCC) (Samstein et al., Nature Genetics, 2019). Results: Any CDK12 and known or likely deleterious CDK12 mutations were identified in 598(3.8%) and 98(0.62%) patients, respectively. Across all cancer types, prostate adenocarcinoma(PRAD) was found to have the highest frequency of deleterious mutations(8.75%, 23/263), followed by breast cancer (4.97%, 25/503). Mutations were also detected in multiple cancer types including bladder cancer, ovarian cancer, lung cancer, colorectal cancer and so on with a frequency of less than 1%. CDK12 mutations were associated with shorter OS (HR = 15.25; 95% CI, 2.88-80.73; p < 0.001) in TCGA PRAD and cholangiocarcinoma datasets, which was not seen in other cancer types. Patients harboring CDK12 mutation had a significant higher TMB(p < 0.001) in the pan-cancer study of publicly-available cohort from MSKCC. Conclusions: CDK12 alterations existed across tumor types in Chinese patients with relatively high frequencies detected in PRAD and breast cancer and represent extremely rare events in multiple cancers. CDK12 mutation was a poor prognostic factor in PRAD and cholangiocarcinoma. In a pan cancer analysis patients with CDK12 mutation tended to have a significant higher TMB and may benefit from PD-1/L1 blockade immunotherapy.

scholarly journals 1963P A pan-cancer study of GNAQ/GNA11 mutations in Chinese cancer patients

2020 ◽  
Vol 31 ◽  
pp. S1104-S1105
Author(s):  
H. Yang ◽  
H. Zhu ◽  
H. Li ◽  
D. Wang ◽  
T. Ma ◽  
...  
Keyword(s):  
Cancer Patients ◽  
Cancer Study ◽  
Chinese Cancer Patients ◽  
Pan Cancer

Hepatocellular carcinoma with ARID1A mutation is associated with higher TMB and poor survival.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16667-e16667 ◽  
Author(s):  
Yaorong Peng ◽  
Bowen Gao ◽  
Zhenyu Zhou ◽  
Tingting Chen ◽  
Wenzhuan Xie ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Cancer Patients ◽  
Gene Mutation ◽  
Sequencing Data ◽  
Coding Region ◽  
Poor Prognostic Factor ◽  
Synonymous Mutations ◽  
Significant Difference ◽  
Chinese Cohort ◽  
Pan Cancer

e16667 Background: Hepatocellular carcinoma (HCC) is a heterogeneous disease that lacks molecular predictors of response to available treatments. AT-rich interactive domain 1A (ARID1A), a SWI/SNF chromatin remodeling gene, is commonly mutated in human cancers and hypothesized to be a tumor suppressor gene. In recent years, immune checkpoint blockade immunotherapies (ICIs) are promising therapies for multiple cancers including HCC, and tumor mutation burden (TMB) was an important biomarker to predict the efficacy of ICIs. Besides, previous research reported that ARID1A deficiency was associated with mismatch repair (MMR) in cancer, and may cooperated with ICIs. Methods: Whole exome sequencing data of 10336 pan-cancer patients including 353 HCC patients was obtained from the Cancer Genome Altas (TCGA). Next generation sequencing (NGS) data of 15849 pan-cancer patients including 1926 HCC patients from Chinese clinical dataset were analyzed to explore the correlation between ARID1A gene mutation and TMB. TMB was defined as total number of somatic non-synonymous mutations in coding region. Prognostic data of 136 HCC patients were obtained from the MSK-IMPACT Clinical Sequencing Cohort (MSKCC). Results: In total, 8.62% (891/10336) of pan-cancer patients in TCGA harboring ARID1A mutation and 8.47% (3188/37628) in Chinese cohort, while mutant percentage of HCC was 9.35% (33/353) in TCGA, 9.03% (174/1926) in Chinese cohort, the alternation frequency of ARID1A in two cohorts was no significant difference (P = 0.3334). The medium TMB level of ARID1A mutant group was higher than wild-type group with significant difference both in Chinese pan-cancer and HCC (medium TMB level, P < 0.0001). Results of 18 kinds of ARID1A mutated tumors patients in TCGA cohort indicated that ARID1A mutation was an independent risk factor in liver cancer affecting overall survival (OS, HR 2.43, 95% IC 1.07-5.54, P = 0.0286). Besides, Kaplan-Meier analysis was performed on HCC patients in MSKCC cohort, ARID1A statue resulted in significantly shorter OS (median, 12.2 vs 21.43 months; HR 2.5; P = 0.0092). Conclusions: The results indicated that ARID1A gene mutation was a poor prognostic factor in hepatocellular carcinoma, and these mutational states were associated with higher TMB level, which might be a potential positive biomarker of immunotherapy.

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