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ABSTRACT 5–10% of total prostate cancer (PCa) cases are hereditary. Particularly, immune checkpoint inhibitor-sensitive tandem duplicator phenotype (TDP) accounts for 6.9% of PCa cases,

whereas genetic susceptibility genes remain completely unknown. We identified a Chinese family with two PCa patients, in which the PCa phenotype co-segregated with a rare germline variant

EGFRR831H. Patient-derived conditionally reprogrammed cells (CRC) exhibited increased EGFR and AKT phosphorylation, and a sensitivity to EGFR antagonist Afatinib in migration assays,

suggesting the EGFR allele was constitutively active. Both EGFRR831H-mutant tumours contained biallelic CDK12 inactivation, together with prominent tandem duplication across the genome.

These somatic mutations could be detected in urine before surgery. Analysis of public databases showed a significant correlation between the mutation status of EGFR and CDK12. Taken

together, our genetic and functional analyses identified a previously undescribed link between EGFR and PCa. Access through your institution Buy or subscribe This is a preview of

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PROSTATE CANCERS OF AFRICAN AMERICAN MEN IS ASSOCIATED WITH RAPID DISEASE PROGRESSION Article Open access 19 September 2024 EXTENSIVE GERMLINE-SOMATIC INTERPLAY CONTRIBUTES TO PROSTATE

CANCER PROGRESSION THROUGH HNF1B CO-OPTION OF TMPRSS2-ERG Article Open access 28 November 2022 ACQUIRED COPY NUMBER VARIATION IN PROSTATE TUMOURS: A REVIEW OF COMMON SOMATIC COPY NUMBER

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gene mutations. Cancer Cell. 2018;34:197–210.e195. Article  CAS  PubMed  PubMed Central  Google Scholar  Download references ACKNOWLEDGEMENTS We thank the patients and their family members

for participating in our study. We gratefully acknowledge excellent technical assistance provided by Ms. Yuan Zhu, Ms. Shanshan Zhang, and Ms. Yayun Fang from Zhongnan Hospital of Wuhan

University. We would like to acknowledge the TCGA and COSMIC databases for providing use of data free of charge. We also thank International Science Editing

(http://www.internationalscienceediting.com) for editing this manuscript. FUNDING This study was supported in part by grants from the Health commission of Hubei Province scientific research

project (WJ2019H080), Chinese Central Special Fund for Local Science and Technology Development of Hubei Province (2018ZYYD023), Science and Technology Department of Hubei Province Key

Project (2018ACA159), and Wuhan Science and Technology Bureau Key Project (2018061005132294). The funders had no role in study design, data collection and analysis, decision to publish, or

preparation of the manuscript. AUTHOR INFORMATION Author notes * These authors contributed equally: Kaiyu Qian, Gang Wang, Lingao Ju AUTHORS AND AFFILIATIONS * Department of Urology,

Zhongnan Hospital of Wuhan University, Wuhan, China Kaiyu Qian, Yongwen Luo, Yejinpeng Wang, Tianchen Peng, Yu Xiao & Xinghuan Wang * Department of Biological Repositories, Zhongnan

Hospital of Wuhan University, Wuhan, China Kaiyu Qian, Gang Wang, Lingao Ju & Yu Xiao * Human Genetic Resources Preservation Center of Hubei Province, Wuhan, China Kaiyu Qian, Gang Wang,

 Lingao Ju & Yu Xiao * Laboratory of Precision Medicine, Zhongnan Hospital of Wuhan University, Wuhan, China Gang Wang, Lingao Ju & Yu Xiao * Department of Biotherapy, Cancer Center,

West China Hospital of Sichuan University, Chengdu, China Jiyan Liu * Center of Life Sciences, Peking University, Beijing, China Fangjin Chen & Yi Zhang * Euler Technology, Beijing,

China Yi Zhang * Medical Research Institute, Wuhan University, Wuhan, China Xinghuan Wang Authors * Kaiyu Qian View author publications You can also search for this author inPubMed Google

Scholar * Gang Wang View author publications You can also search for this author inPubMed Google Scholar * Lingao Ju View author publications You can also search for this author inPubMed 

Google Scholar * Jiyan Liu View author publications You can also search for this author inPubMed Google Scholar * Yongwen Luo View author publications You can also search for this author

inPubMed Google Scholar * Yejinpeng Wang View author publications You can also search for this author inPubMed Google Scholar * Tianchen Peng View author publications You can also search for

this author inPubMed Google Scholar * Fangjin Chen View author publications You can also search for this author inPubMed Google Scholar * Yi Zhang View author publications You can also

search for this author inPubMed Google Scholar * Yu Xiao View author publications You can also search for this author inPubMed Google Scholar * Xinghuan Wang View author publications You can

also search for this author inPubMed Google Scholar CORRESPONDING AUTHORS Correspondence to Yi Zhang or Xinghuan Wang. ETHICS DECLARATIONS CONFLICT OF INTEREST The authors declare that they

have no conflict of interest. STATEMENT OF PATIENT CONSENT All PCa patients, family members of the PCa pedigree, and additional cancer patients, provided written informed consent. All study

procedures were performed in accordance with the ethical standards of the Institutional Ethics Review Committee. ADDITIONAL INFORMATION PUBLISHER’S NOTE Springer Nature remains neutral with

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ARTICLE CITE THIS ARTICLE Qian, K., Wang, G., Ju, L. _et al._ A novel germline EGFR variant p.R831H causes predisposition to familial CDK12-mutant prostate cancer with tandem duplicator

phenotype. _Oncogene_ 39, 6871–6878 (2020). https://doi.org/10.1038/s41388-020-01476-9 Download citation * Received: 15 March 2020 * Revised: 02 September 2020 * Accepted: 15 September 2020

* Published: 25 September 2020 * Issue Date: 29 October 2020 * DOI: https://doi.org/10.1038/s41388-020-01476-9 SHARE THIS ARTICLE Anyone you share the following link with will be able to

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