Universal screening for Lynch syndrome in a large consecutive cohort of Chinese colorectal cancer patients: High prevalence and unique molecular features
Wu Jiang
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
W.J., M.C., S.L., and J.B. contributed equally to this workSearch for more papers by this authorMu-Yan Cai
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
W.J., M.C., S.L., and J.B. contributed equally to this workSearch for more papers by this authorShi-Yong Li
BGI-Guangzhou Medical Laboratory, BGI-Shenzhen, People's Republic of China
W.J., M.C., S.L., and J.B. contributed equally to this workSearch for more papers by this authorJin-Xin Bei
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
W.J., M.C., S.L., and J.B. contributed equally to this workSearch for more papers by this authorFang Wang
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Search for more papers by this authorHeather Hampel
Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
Search for more papers by this authorYi-Hong Ling
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Search for more papers by this authorIan M. Frayling
Institute of Cancer and Genetics, Cardiff University, Cardiff, United Kingdom
All-Wales Medical Genetics Service, Institute of Medical Genetics, University Hospital of Wales, Cardiff, United Kingdom
Search for more papers by this authorFrank A. Sinicrope
Department of Oncology, Mayo Clinic, Rochester, MN
Search for more papers by this authorMiguel A. Rodriguez-Bigas
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Search for more papers by this authorJames J. Dignam
Department of Public Health Sciences, The University of Chicago Biological Sciences, Chicago, IL
Search for more papers by this authorDavid J. Kerr
Department of Clinical Pharmacology, OCRB, Churchill Campus, Headington, University of Oxford, Oxford, United Kingdom
Search for more papers by this authorRafael Rosell
Catalan Institute of Oncology, Germans Trias i Pujol Health Sciences Institute and Hospital, Badalona, Barcelona, Spain
Search for more papers by this authorMao Mao
BGI-Guangzhou Medical Laboratory, BGI-Shenzhen, People's Republic of China
Search for more papers by this authorJi-Bin Li
Department of Clinical Research, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Search for more papers by this authorYun-Miao Guo
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Search for more papers by this authorXiao-Yan Wu
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Search for more papers by this authorLing-Heng Kong
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Search for more papers by this authorJing-Hua Tang
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Search for more papers by this authorXiao-Dan Wu
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Search for more papers by this authorChao-Feng Li
Department of Information Technology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Search for more papers by this authorJie-Rong Chen
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Search for more papers by this authorQing-Jian Ou
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Search for more papers by this authorMing-Zhi Ye
BGI-Guangzhou Medical Laboratory, BGI-Shenzhen, People's Republic of China
Search for more papers by this authorFeng-Ming Guo
BGI-Guangzhou Medical Laboratory, BGI-Shenzhen, People's Republic of China
Search for more papers by this authorPeng Han
BGI-Guangzhou Medical Laboratory, BGI-Shenzhen, People's Republic of China
Search for more papers by this authorQi-Wei Wang
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, People's Republic of China
Search for more papers by this authorDe-Sen Wan
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Search for more papers by this authorLi Li
Imaging Diagnosis and Interventional Center, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Search for more papers by this authorCorresponding Author
Rui-Hua Xu
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Correspondence to: Prof. Pei-Rong Ding, Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, People's Republic of China, E-mail: [email protected]; Tel.: +86 20 87343920; or Prof. Rui-Hua Xu, Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, People's Republic of China, E-mail: [email protected]; or Prof. Zhi-Zhong Pan, Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, People's Republic of China, E-mail: [email protected]Search for more papers by this authorCorresponding Author
Zhi-Zhong Pan
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Correspondence to: Prof. Pei-Rong Ding, Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, People's Republic of China, E-mail: [email protected]; Tel.: +86 20 87343920; or Prof. Rui-Hua Xu, Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, People's Republic of China, E-mail: [email protected]; or Prof. Zhi-Zhong Pan, Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, People's Republic of China, E-mail: [email protected]Search for more papers by this authorCorresponding Author
Pei-Rong Ding
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Correspondence to: Prof. Pei-Rong Ding, Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, People's Republic of China, E-mail: [email protected]; Tel.: +86 20 87343920; or Prof. Rui-Hua Xu, Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, People's Republic of China, E-mail: [email protected]; or Prof. Zhi-Zhong Pan, Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, People's Republic of China, E-mail: [email protected]Search for more papers by this authorWritten on behalf of AME Colorectal Cancer Cooperative Group
Search for more papers by this authorWu Jiang
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
W.J., M.C., S.L., and J.B. contributed equally to this workSearch for more papers by this authorMu-Yan Cai
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
W.J., M.C., S.L., and J.B. contributed equally to this workSearch for more papers by this authorShi-Yong Li
BGI-Guangzhou Medical Laboratory, BGI-Shenzhen, People's Republic of China
W.J., M.C., S.L., and J.B. contributed equally to this workSearch for more papers by this authorJin-Xin Bei
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
W.J., M.C., S.L., and J.B. contributed equally to this workSearch for more papers by this authorFang Wang
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Search for more papers by this authorHeather Hampel
Division of Human Genetics, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA
Search for more papers by this authorYi-Hong Ling
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Pathology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Search for more papers by this authorIan M. Frayling
Institute of Cancer and Genetics, Cardiff University, Cardiff, United Kingdom
All-Wales Medical Genetics Service, Institute of Medical Genetics, University Hospital of Wales, Cardiff, United Kingdom
Search for more papers by this authorFrank A. Sinicrope
Department of Oncology, Mayo Clinic, Rochester, MN
Search for more papers by this authorMiguel A. Rodriguez-Bigas
Department of Surgical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX
Search for more papers by this authorJames J. Dignam
Department of Public Health Sciences, The University of Chicago Biological Sciences, Chicago, IL
Search for more papers by this authorDavid J. Kerr
Department of Clinical Pharmacology, OCRB, Churchill Campus, Headington, University of Oxford, Oxford, United Kingdom
Search for more papers by this authorRafael Rosell
Catalan Institute of Oncology, Germans Trias i Pujol Health Sciences Institute and Hospital, Badalona, Barcelona, Spain
Search for more papers by this authorMao Mao
BGI-Guangzhou Medical Laboratory, BGI-Shenzhen, People's Republic of China
Search for more papers by this authorJi-Bin Li
Department of Clinical Research, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Search for more papers by this authorYun-Miao Guo
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Search for more papers by this authorXiao-Yan Wu
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Molecular Diagnostics, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Search for more papers by this authorLing-Heng Kong
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Search for more papers by this authorJing-Hua Tang
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Search for more papers by this authorXiao-Dan Wu
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Search for more papers by this authorChao-Feng Li
Department of Information Technology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Search for more papers by this authorJie-Rong Chen
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Search for more papers by this authorQing-Jian Ou
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Search for more papers by this authorMing-Zhi Ye
BGI-Guangzhou Medical Laboratory, BGI-Shenzhen, People's Republic of China
Search for more papers by this authorFeng-Ming Guo
BGI-Guangzhou Medical Laboratory, BGI-Shenzhen, People's Republic of China
Search for more papers by this authorPeng Han
BGI-Guangzhou Medical Laboratory, BGI-Shenzhen, People's Republic of China
Search for more papers by this authorQi-Wei Wang
State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-sen University, Guangzhou, People's Republic of China
Search for more papers by this authorDe-Sen Wan
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Search for more papers by this authorLi Li
Imaging Diagnosis and Interventional Center, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Search for more papers by this authorCorresponding Author
Rui-Hua Xu
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Medical Oncology, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Correspondence to: Prof. Pei-Rong Ding, Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, People's Republic of China, E-mail: [email protected]; Tel.: +86 20 87343920; or Prof. Rui-Hua Xu, Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, People's Republic of China, E-mail: [email protected]; or Prof. Zhi-Zhong Pan, Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, People's Republic of China, E-mail: [email protected]Search for more papers by this authorCorresponding Author
Zhi-Zhong Pan
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Correspondence to: Prof. Pei-Rong Ding, Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, People's Republic of China, E-mail: [email protected]; Tel.: +86 20 87343920; or Prof. Rui-Hua Xu, Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, People's Republic of China, E-mail: [email protected]; or Prof. Zhi-Zhong Pan, Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, People's Republic of China, E-mail: [email protected]Search for more papers by this authorCorresponding Author
Pei-Rong Ding
Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China; Collaborative Innovation Center for Cancer Medicine, Guangzhou, China
Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, Guangzhou, People's Republic of China
Correspondence to: Prof. Pei-Rong Ding, Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, People's Republic of China, E-mail: [email protected]; Tel.: +86 20 87343920; or Prof. Rui-Hua Xu, Department of Medical Oncology, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, People's Republic of China, E-mail: [email protected]; or Prof. Zhi-Zhong Pan, Department of Colorectal Surgery, Sun Yat-sen University Cancer Center, 651 Dongfeng East Road, Guangzhou 510060, People's Republic of China, E-mail: [email protected]Search for more papers by this authorWritten on behalf of AME Colorectal Cancer Cooperative Group
Search for more papers by this authorAbstract
The prevalence of Lynch syndrome (LS) varies significantly in different populations, suggesting that ethnic features might play an important role. We enrolled 3330 consecutive Chinese patients who had surgical resection for newly diagnosed colorectal cancer. Universal screening for LS was implemented, including immunohistochemistry for mismatch repair (MMR) proteins, BRAFV600E mutation test and germline sequencing. Among the 3250 eligible patients, MMR protein deficiency (dMMR) was detected in 330 (10.2%) patients. Ninety-three patients (2.9%) were diagnosed with LS. Nine (9.7%) patients with LS fulfilled Amsterdam criteria II and 76 (81.7%) met the revised Bethesda guidelines. Only 15 (9.7%) patients with absence of MLH1 on IHC had BRAFV600E mutation. One third (33/99) of the MMR gene mutations have not been reported previously. The age of onset indicates risk of LS in patients with dMMR tumors. For patients older than 65 years, only 2 patients (5.7%) fulfilling revised Bethesda guidelines were diagnosed with LS. Selective sequencing of all cases with dMMR diagnosed at or below age 65 years and only of those dMMR cases older than 65 years who fulfill revised Bethesda guidelines results in 8.2% fewer cases requiring germline testing without missing any LS diagnoses. While the prevalence of LS in Chinese patients is similar to that of Western populations, the spectrum of constitutional mutations and frequency of BRAFV600E mutation is different. Patients older than 65 years who do not meet the revised Bethesda guidelines have a low risk of LS, suggesting germline sequencing might not be necessary in this population.
Abstract
What's new?
The prevalence of Lynch syndrome (LS) varies significantly in different ethnic populations. In this study, the authors screened more than 3000 Chinese colorectal cancer patients for mutations associated with LS, including mismatch repair (MMR) and BRAFV600E mutations. They found that, while the prevalence of LS in Chinese patients is similar to that of Western populations, the spectrum of mutations is different, including many not previously reported. Older patients had a decreased risk of LS, suggesting that germline sequencing may not be necessary in this population.
Supporting Information
| Filename | Description |
|---|---|
| ijc32044-sup-0001-supinfo.docxWord 2007 document , 49.7 KB |
Table S1 eTable1. Characteristics of the 93 patients with pathogenic or likely pathogenic mutations eTable2. Characteristics of the 29 missense variants of uncertain significance consistent with immunohistochemistry results eFigure. Percentage of different sequence variants observed in the MLH1, MSH2, MSH6, PMS2 and EPCAM genes from a total of 97 variants. |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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