J Cancer 2018; 9(13):2302-2307. doi:10.7150/jca.24932
The Tumor Mutational Burden of Chinese Advanced Cancer Patients Estimated by a 381-cancer-gene Panel
1. Department of Medical Thoracic Oncology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fujian, P.R. China.
2. Department of Oncology, Chinese PLA General Hospital, Beijing, P.R. China.
3. Department of Interventional Radiology, the Second Clinical Medical College (Shenzhen People's Hospital), Jinan University, Shenzhen, P.R. China.
4. The medical department, 3D Medicine Inc. Shanghai, P.R. China.
5. The bioinformatics department, 3D Medicine Inc. Shanghai, P.R. China.
6. Department of Thoracic Disease Center, Zhejiang Rongjun Hospital, Zhejiang, P.R. China.
7. Department of Pathology, Fujian Cancer Hospital, Fujian Medical University Cancer Hospital, Fujian, P.R. China.
8. Transplantation Center, Department of Transplant Surgery, The First Affiliated Hospital, Sun Yet-sen University, Guangzhou, P. R. China.
9. Oncology Department, East Hospital Affiliated to Shanghai Tongji University, Shanghai, P.R. China.
10. Department of medical oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, P.R. China.
Zhuang W, Ma J, Chen X, Wang G, Lu J, Chen Y, Dong H, Cai S, Zhang Y, Zhao X, Zhu Y, Xu C, Huang Y, Huang Z, Zhu X, Jiang H, Wang Z. The Tumor Mutational Burden of Chinese Advanced Cancer Patients Estimated by a 381-cancer-gene Panel. J Cancer 2018; 9(13):2302-2307. doi:10.7150/jca.24932. Available from http://www.jcancer.org/v09p2302.htm
Purpose: Tumor mutational burden (TMB) calculated by whole-exome sequencing (WES) is proved to be effective to predict the clinical benefit of immune checkpoint blockades. However, WES is not commonly used in China. We aimed to determine if a 381-caner-gene panel (CGP) could be used to estimate TMB, delineate the landscape of TMB of Chinese patients and identify mutated genes and pathways related to higher TMB.
Methods: We first evaluated the correlation between the TMB estimated by a 381-cancer-gene panel MasterView and WES using the data from the melanoma sample cohort. 3023 formalin fixed, paraffin-embedded tumor specimens from 2932 Chinese patients with advanced solid tumor were profiled for 381 gene sequencing, the baits of which covered 4,557 exons of 365 cancer-related genes and 47 introns of 25 genes frequently rearranged in cancer (All performed in a lab who achieved full marks five times in the external quality assessment by College of American Pathologists [CAP]). Using the sequencing data, we estimated the TMB of Chinese advanced solid tumor and identified mutated genes and pathways related to higher TMB level.
Results: 381-CGP-mutational burden was strongly associated with those calculated by WES (R2 = 0.978). The median TMB for each tumor type was 5.65 (colorectal cancer), 4.84 (lung cancer), 4.03 (hepatobiliary cancer), 4.03 (gastric carcinoma), 4.03 (breast cancer) mutations/mb respectively. No correlation was observed between TMB level and age (P = 0.577) or gender (P = 0.307). The TMB of patients with mismatch repair (MMR) or DNA repair response (DDR) pathway deficiency was significantly higher than that without MMR or DDR pathway deficiency (P < 0.001).
Conclusion: The 381-cancer gene panel is a clinical practicable method to assess tumor mutational burden compared with whole exome sequencing. MMR and DDR deficiency are correlated with higher tumor mutational burden of Chinese patients with advanced solid tumors.
Keywords: Tumor mutational burden, cancer-gene panel, mismatch repair, DNA damage response