Expert consensus on the detection and clinical application of tumor mutational burden

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Zhenying Guo^{¹^,^*}, Chunwei Xu^{²^,^*}, Shirong Zhang^{³^,^*}, Yue Hao^{⁴^,^*}, Xiaotong Hu^⁵, Ming Zhao^⁶, Chan Xiang^⁷, Yingshi Piao^⁸, Pingli Sun^⁹, Xueping Xiang^¹⁰, Jing Zhao^¹¹, Huanwen Wu^¹², Weixing Li^¹³, Jinpu Yu^¹⁴, Jingping Yuan^¹⁵, Shuangshuang Wang^¹⁶, Cong Wang^¹⁷, Yun Gu^¹⁸, Bingjian Lv^¹⁹, Liping Zhang^²⁰, Yueping Liu^²¹, Xiaobin Cui^²², Weizhong Gu^²³, Yining Li^²⁴, Wei Wang^²⁵, Wenjun Yang^²⁶, Weiguo Long^²⁷, Jingjing Xiang^²⁸, Hong Mou^²⁹, Biao Liu^³⁰, Huajuan Ruan^³¹, Yubin Wang^³², Yongjie Zhu^³³, Feng Wang^³⁴, Zhonghua Wang^³⁵, Xiaomin Feng^¹⁸, Xing Liu^³⁶, Peng Li^³⁷, Min Deng^³⁸, Bin Lian^³⁹, Lili Mao^³⁹, Qian Wang^⁴⁰, Wenxian Wang^⁴, Zhengbo Song^⁴, Ziming Li^⁴¹, Wenzhao Zhong^⁴², Zhijie Wang^⁴³, Shengxiang Ren^⁴⁴, Wenfeng Fang^⁴⁵, Yongchang Zhang^⁴⁶, Jingjing Liu^⁴⁷, Xiuyu Cai^⁴⁸, Anwen Liu^⁴⁹, Wen Li^⁵⁰, Ping Zhan^⁵¹, Hongbing Liu^⁵¹, Tangfeng Lv^⁵¹, Liyun Miao^⁵², Lingfeng Min^⁵³, Yu Chen^⁵⁴, Yu Zhang^⁵⁵, Feng Wang^⁵⁶, Zhansheng Jiang^⁵⁷, Gen Lin^⁵⁴, Long Huang^⁴⁹, Xingxiang Pu^⁵⁸, Rongbo Lin^⁵⁴, Weifeng Liu^⁵⁹, Chuangzhou Rao^⁶⁰, Dongqing Lv^⁶¹, Zongyang Yu^⁶², Peng Shen^⁶³, Xiaoyan Li^⁶⁴, Chuanhao Tang^⁶⁵, Chengzhi Zhou^⁶⁶, Junping Zhang^⁶⁷, Junli Xue^⁶⁸, Hui Guo^⁶⁹, Qian Chu^⁷⁰, Rui Meng^⁷¹, Jingxun Wu^⁷², Rui Zhang^⁷³, Jin Zhou^⁷⁴, Zhengfei Zhu^⁷⁵, Yongheng Li^⁷⁶, Hong Qiu^⁷⁰, Fan Xia^⁷⁵, Yuanyuan Lu^⁷⁷, Xiaofeng Chen^⁷⁸, Rui Ge^⁷⁹, Enyong Dai^⁸⁰, Yu Han^⁸¹, Jian Zhang^⁸², Yinghua Ji^⁸³, Xianbin Liang^⁸⁴, Hongmei Zhang^⁸⁵, Xuelei Ma^⁸⁵, Xuewen Liu^⁸⁶, Yu Yao^⁸⁷, Peng Luo^⁸², Weiwei Pan^⁸⁸, Fei Pang^⁸⁹, Fan Wu^⁹⁰, Dejian Gu^⁹¹, Li Wang^⁹¹, Liping Wang^⁹², Youcai Zhu^⁹³, Li Lin^⁶⁵, Weiwen Li^⁹⁴, Xinqing Lin^⁶⁶, Jing Cai^⁴⁹, Ling Xu^⁹⁵, Jisheng Li^⁹⁶, Xiaodong Jiao^⁹⁷, Kainan Li^⁹⁸, Jia Wei^⁹⁹, Huijing Feng^⁶⁷, Lin Wang^¹⁰⁰, Yingying Du^¹⁰¹, Wang Yao^¹⁰², Xuefei Shi^¹⁰³, Xiaomin Niu^⁴¹, Dongmei Yuan^⁵¹, Yanwen Yao^⁵¹, Yinbin Zhang^⁶⁹, Binbin Song^¹⁰⁴, Wenfeng Li^¹⁰⁵, Jianfei Fu^¹⁰⁶, Hong Wang^¹⁰⁷, Mingxiang Ye^⁵¹, Dong Wang^⁵¹, Zhaofeng Wang^⁵¹, Qing Ji^⁴, Yuan Fang^¹⁰⁸, Qing Wei^⁴, Zhen Wang^¹⁰⁹, Bin Wan^¹¹⁰, Donglai Lv^¹¹¹, Xiaofeng Li^⁹³, Shengjie Yang^¹¹², Jing Kang^⁴², Jiatao Zhang^⁴², Chao Zhang^⁴², Lin Shi^¹¹³, Yina Wang^¹¹⁴, Bihui Li^¹¹⁵, Zhang Zhang^¹¹⁶, Ke Wang^{¹¹⁷^,¹¹⁸}, Zhefeng Liu^¹⁰⁷, Nong Yang^⁴⁶, Lin Wu^⁵⁸, Xiaobing Chen^¹¹⁹, Gu Jin^¹²⁰, Zhongwu Li^¹²¹, Miao Li^¹²², Guansong Wang^¹²³, Jiandong Wang^¹²⁴, Meiyu Fang^⁴, Yong Fang^¹²⁵, Xiaojia Wang^⁴, Jing Chen^⁷¹, Yiping Zhang^⁴, Xixu Zhu^¹⁰⁹, Yi Shen^¹²⁶, Shenglin Ma^¹²⁷, Biyun Wang^¹²⁸, Lu Si^³⁹, Yong Song^⁵¹, Yuanzhi Lu^¹²⁹

(

), Aijun Liu^¹³⁰(

), Yuchen Han^⁷

(

)

Cancer Center, Department of Pathology, Zhejiang Provincial People’s Hospital (Affiliated People’s Hospital), Hangzhou Medical College, Hangzhou 310014, China

Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou 310022, China

Translational Medicine Research Center, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou First People’s Hospital, Cancer Center, Westlake University School of Medicine, Hangzhou 310006, China

Department of Chemotherapy, Chinese Academy of Sciences University Cancer Hospital (Zhejiang Cancer Hospital), Hangzhou 310022, China

Department of Pathology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China

Ningbo Clinical Pathology Diagnosis Center, Ningbo 315100, China

Department of Pathology, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China

Department of Pathology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, China

Department of Pathology, The Second Hospital of Jilin University, Changchun 130041, China

Department of Pathology, The Second Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310009, China

Department of Pathology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310003, China

Department of Pathology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100730, China

Laboratory Medicine Center, Zhejiang Center for Clinical Laboratory, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou 310014, China

Department of Cancer Molecular Diagnostics Core, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China

Department of Pathology, Renmin Hospital of Wuhan University, Wuhan 430060, China

Department of Pathology, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China

Department of Pathology, The First Affiliated Hospital of Nanjing Medical University (Jiangsu Province Hospital), Nanjing 210029, China

Department of Pathology, Women’s Hospital of Nanjing Medical University, Nanjing Women and Children’s Healthcare Hospital, Nanjing 210004, China

Department of Surgical Pathology Women’s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, of China

Department of Pathology, Shanghai Pudong Hospital, School of Medicine, Fudan University, Shanghai 201399, China

Department of Pathology, The Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, China

Department of Pathology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing 210008, China

Department of Pathology, Children’s Hospital Zhejiang University School of Medicine, Hangzhou 310005, China

Department of Pathology, Stomatology Hospital, School of Stomatology, Zhejiang University, Hangzhou 310000, China

Department of Pathology, Tongde Hospital of Zhejiang Province, Hangzhou 310012, China

Department of Pathology, Affiliated Hospital of Hangzhou Normal University, Hangzhou 310000, China

Department of Pathology, The People’s Hospital of Leshan, Leshan 614000, China

Department of Pathology, Affiliated Hangzhou First People’s Hospital, Westlake University School of Medicine, Hangzhou 310006, China

Department of Pathology, Chun’an First People’s Hospital, Hangzhou 311700, China

Department of Pathology, The Affiliated Suzhou Hospital, Nanjing Medical University, Suzhou 215006, China

Department of Pathology, The First People’s Hospital of Hangzhou Lin’an District, Affiliated Lin’an People’s Hospital, Hangzhou Medical College, Hangzhou 311300, China

Department of Pathology, Tiantai County People’s Hospital, Taizhou 317200, China

Department of Pathology, First People’s Hospital of Aksu, Aksu 843000, China

Department of Pathology, Xianju People’s Hospital, Zhejiang Southeast Campus of Zhejiang Provincial People’s Hospital, Affiliated Xianju’s Hospital, Hangzhou Medical College, Taizhou 317300, China

Department of Pathology, Dinghai Branch of Zhejiang Provincial People’s Hospital, Zhoushan 316000, China

Department of Pathology, Shulan (Hangzhou) Hospital, Hangzhou 310022, China

Department of Pathology, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China

Department of Pathology, Zhejiang Provincial People’s Hospital (Fuyang Campus), Hangzhou 311400, China

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Melanoma and Sarcoma, Peking University Cancer Hospital & Institute, Beijing 100142, China

Department of Respiratory Medicine, Affiliated Hospital of Nanjing University of Chinese Medicine, Jiangsu Province Hospital of Chinese Medicine, Nanjing 210029, China

Department of Shanghai Lung Cancer Center, Shanghai Chest Hospital, Shanghai Jiao Tong University, Shanghai 200030, China

Guangdong Lung Cancer Institute, Guangdong Provincial Laboratory of Translational Medicine in Lung Cancer, Guangdong Provincial People’s Hospital, Guangdong Academy of Medical Sciences, School of Medicine, Guangzhou 510080, China

State Key Laboratory of Molecular Oncology, Department of Medical Oncology, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100021, China

Department of Medical Oncology, Shanghai Pulmonary Hospital, School of Medicine, Tongji University, Shanghai 200433, China

Department of Medical Oncology, Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China

Department of Medical Oncology, Lung Cancer and Gastrointestinal Unit, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China

Department of Thoracic Cancer, Jilin Cancer Hospital, Changchun 130012, China

Department of VIP Inpatient, Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou 510060, China

Department of Oncology, Second Affiliated Hospital of Nanchang University, Nanchang 330006, China

Key Laboratory of Respiratory Disease of Zhejiang Province, Department of Respiratory and Critical Care Medicine, Second Affiliated Hospital of Zhejiang University School of Medicine, Cancer Center, Zhejiang University, Hangzhou 310009, China

Department of Respiratory Medicine, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China

Department of Respiratory Medicine, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210008, China

Department of Respiratory Medicine, Clinical Medical School of Yangzhou University, Subei People’s Hospital of Jiangsu Province, Yangzhou 225001, China

Department of Medical Oncology, Fujian Medical University Cancer Hospital & Fujian Cancer Hospital, Fuzhou 350014, China

Department of Oncology, Guizhou Provincial People’s Hospital, Guiyang 550001, China

Department of Internal Medicine, Cancer Center of PLA, Qinhuai Medical Area, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China

Department of Integrative Oncology, Tianjin Medical University Cancer Institute and Hospital, Tianjin 300060, China

The Second Department of Thoracic Oncology, Hunan Cancer Hospital/The Affiliated Cancer Hospital of Xiangya School of Medicine, Central South University, Changsha 410013, China

Department of Orthopedic Oncology Surgery, Beijing Ji shui tan Hospital, Peking University, Beijing 100035, China

Department of Radiotherapy and Chemotherapy, Hwamei Hospital, University of Chinese Academy of Sciences, Ningbo 315010, China

Department of Pulmonary Medicine, Taizhou Hospital of Wenzhou Medical University, Taizhou 317000, China

Department of Respiratory Medicine, the 900th Hospital of the Joint Logistics Team (the Former Fuzhou General Hospital), Fujian Medical University, Fuzhou 350025, China

Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou 510515, China

Department of Oncology, Beijing Tiantan Hospital, Capital Medical University, Beijing 100700, China

Department of Medical Oncology, Peking University International Hospital, Beijing 102206, China

State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou 510300, China

Department of Thoracic Oncology, Shanxi Academy of Medical Sciences, Shanxi Bethune Hospital, Taiyuan 030032, China

Department of Oncology, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai 200123, China

Department of Oncology, The Second Affiliated Hospital of Medical College, Xi’an Jiaotong University, Xi’an 710004, China

Department of Oncology, Tongji Hospital of Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China

Cancer Center, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China

Department of Medical Oncology, The First Affiliated Hospital of Medicine, Xiamen University, Xiamen 361003, China

Department of Medical Oncology, Cancer Hospital of China Medical University, Shenyang 110042, China

Department of Medical Oncology, Sichuan Cancer Hospital & Institute, Sichuan Cancer Center, School of Medicine, University of Electronic Science and Technology, Chengdu 610041, China

Department of Radiation Oncology, Fudan University Shanghai Cancer Center, Shanghai 200032, China

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Radiation Oncology, Peking University Cancer Hospital & Institute, Beijing 100142, China

State Key Laboratory of Cancer Biology, National Clinical Research Center for Digestive Diseases and Xijing Hospital of Digestive Diseases, Fourth Military Medical University, Xi’an 710032, China

Department of Oncology, Jiangsu Province Hospital and Nanjing Medical University First Affiliated Hospital, Nanjing 210029, China

Department of General Surgery, Huadong Hospital Affiliated to Fudan University, Shanghai 200040, China

Department of Oncology and Hematology, China-Japan Union Hospital of Jilin University, Changchun 130033, China

Department of Gastrointestinal Oncology, Harbin Medical University Cancer Hospital, Harbin 150081, China

Department of Oncology, Zhujiang Hospital, Southern Medical University, Guangzhou 510282, China

Department of Oncology, The First Affiliated Hospital of Xinxiang Medical University, Xinxiang 453000, China

Department of Oncology, The Third People’s Hospital of Zhengzhou, Zhengzhou 450000, China

Department of Biotherapy, State Key Laboratory of Biotherapy, Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China

Department of Oncology, the Third Xiangya Hospital, Central South University, Changsha 410013, China

Department of Medical Oncology, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an 710061, China

Department of Cell Biology, College of Medicine, Jiaxing University, Jiaxing 314001, China

Department of Medical, Shanghai OrigiMed Co, Ltd, Shanghai 201114, China

Department of Medical, Menarini Silicon Biosystems SpA, Shanghai 200333, China

Department of Medical, Geneplus-Beijing, Beijing 102200, China

Department of Oncology, Baotou Cancer Hospital, Baotou 014000, China

Department of Thoracic Disease Diagnosis and Treatment Center, Zhejiang Rongjun Hospital, The Third Affiliated Hospital of Jiaxing University, Jiaxing 314000, China

Department of Oncology, Lishui Municipal Central Hospital, Lishui 323000, China

Department of Interventional Pulmonary Diseases, Anhui Chest Hospital, Hefei 230011, China

Department of Medical Oncology, Qilu Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250012, China

Department of Medical Oncology, Shanghai Changzheng Hospital, Naval Medical University, Shanghai 200070, China

Department of Oncology, Shandong Provincial Third Hospital, Cheeloo College of Medicine, Shandong University, Jinan 250031, China

Department of The Comprehensive Cancer Center, Affiliated Drum Tower Hospital, Medical School of Nanjing University, Nanjing 210008, China

100

Department of Pathology, Shanxi Academy of Medical Sciences, Shanxi Bethune Hospital, Taiyuan 030032, China

101

Department of Oncology, The First Affiliated Hospital of Anhui Medical University, Hefei 230022, China

102

Department of Interventional Oncology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou 510060, China

103

Department of Respiratory Medicine, Huzhou Hospital, Zhejiang University School of Medicine, Huzhou 313000, China

104

Department of Medical Oncology, The Affiliated Hospital of Jiaxing University, Jiaxing 314000, China

105

Department of Radiation Oncology, First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China

106

Department of Medical Oncology, Affiliated Jinhua Hospital, Zhejiang University School of Medicine, Jinhua 321000, China

107

Senior Department of Oncology, The 5th Medical Center of PLA General Hospital, Beijing 100071, China

108

Department of Pathology, Anhui Provincial Children’s Hospital, Hefei 230051, China

109

Department of Radiation Oncology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China

110

Department of Respiratory Medicine, The Affiliated Jiangning Hospital of Nanjing Medical University, Nanjing 210002, China

111

Department of Clinical Oncology, The 901 Hospital of Joint Logistics Support Force of People Liberation Army, Hefei 230031, China

112

Department of Thoracic Surgery, Chuxiong Yi Autonomous Prefecture People’s Hospital, Chuxiong 675000, China

113

Department of Respiratory Medicine, Zhongshan Hospital, Fudan University, Shanghai 200032, China

114

Department of Oncology, The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou 310000, China

115

Department of Oncology, The Second Affiliated Hospital of Guilin Medical University, Guilin 541199, China

116

International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Discovery of Chinese Ministry of Education (MOE), Guangzhou City Key Laboratory of Precision Chemical Drug Development, School of Pharmacy, Jinan University, Guangzhou 510632, China

117

National Health Commission (NHC) Key Laboratory of Nuclear Medicine, Jiangsu Key Laboratory of Molecular Nuclear Medicine, Jiangsu Institute of Nuclear Medicine, Wuxi 214063, China

118

Department of Radiopharmaceuticals, School of Pharmacy, Nanjing Medical University, Nanjing 210000, China

119

Department of Oncology, The Affiliated Cancer Hospital of Zhengzhou University & Henan Cancer Hospital, Zhengzhou 450008, China

120

Department of Bone and Soft-tissue Surgery, Chinese Academy of Sciences University Cancer Hospital (Zhejiang Cancer Hospital), Hangzhou 310022, China

121

Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Pathology, Peking University Cancer Hospital & Institute, Beijing 100142, China

122

Department of Oncology, The Cancer Hospital of Qinghai Province, Xining 810001, China

123

Institute of Respiratory Diseases, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China

124

Department of Pathology, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China

125

Department of Medical Oncology, Sir Run Run Shaw Hospital, Zhejiang University, Hangzhou 310016, China

126

Department of Thoracic Surgery, Affiliated Jinling Hospital, Medical School of Nanjing University, Nanjing 210002, China

127

Department of Oncology, Key Laboratory of Clinical Cancer Pharmacology and Toxicology Research of Zhejiang Province, Affiliated Hangzhou Cancer Hospital, Cancer Center, Westlake University School of Medicine, Hangzhou 310006, China

128

Department of Breast Cancer and Urological Medical Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China

129

Department of Clinical Pathology, The First Affiliated Hospital of Jinan University, Guangzhou 510630, China

130

Senior Department of Pathology, the 7th Medical Center of PLA General Hospital, Beijing 100700, China

^*These authors contributed equally to this work.

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Abstract

As an emerging biomarker, tumor mutational burden (TMB) has attracted increasing attention from clinicians in predicting the efficacy of tumor immunotherapy. Currently, TMB is detected primarily by whole-exome sequencing or targeted panel sequencing on high-throughput sequencing platforms. However, the lack of uniformity in detection methods, threshold settings, and reporting formats, as well as the significant differences in TMB values among different cancer types, have hindered the standardized application of this biomarker in clinical practice. This consensus focuses on the definition, standardization of detection, clinical significance, and limitations of TMB, and provides consensus recommendations for the clinical application of TMB in real-world practice in China. This consensus is aimed at helping clinicians and laboratory personnel understand the clinical significance and testing standards of TMB, promoting more accurate interpretation of test results, and improving patient care.