Abstract
Activating germline mutations of the MET gene are associated with hereditary papillary renal cancer. This a very rare autosomal dominant condition, which is usually considered not to display a phenotype of multiple types of malignancy. However, this report describes the case of a man who has been affected with testicular teratoma, diffuse large B-cell lymphoma and multiple hepatic cysts, as well as multiple papillary renal cancers. There is good supporting evidence for roles of over-expression/activity of the HGF/MET ligand-receptor in development of these tumours, raising the possibility of other increased cancer risks associated with activating germline MET gene mutations.
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References
Schmidt L, Duh F, Chen F et al (1997) Germline and somatic mutations in the tyrosine kinase domain of the MET proto-oncogene in papillary renal carcinomas. Nat Genet 16:68–73
Carlo MI, Hakimi AA, Stewart GD et al (2019) Familial kidney cancer: implications of new syndromes and molecular insights. Eur Urol 76:754–764
Tovar EA, Graveel CR (2017) MET in human cancer: germline and somatic mutations. Ann Transl Med 5:205
Cancer Research UK (2018) Testicular cancer risk. https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/testicular-cancer/risk-factors. Accessed 8th April 2020
Cancer Research UK (2018) Non-Hodgkin lymphoma risk. https://www.cancerresearchuk.org/health-professional/cancer-statistics/statistics-by-cancer-type/non-hodgkin-lymphoma/risk-factors. Accessed 8th April 2020
Ricci G, Catizone A (2014) Pleiotropic activities of HGF/c-Met system in testicular physiology: paracrine and endocrine implications. Front Endocrinol 5:38
Scheri KC, Leonetti E, Laino L et al (2018) c-MET receptor as potential biomarker and target molecule for malignant testicular germ cell tumors. Oncotarget 9:31842–31860
Das MK, Kleppa L, Haugen TB (2019) Functions of genes related to testicular germ cell tumour development. Andrology 7:527–535
Zeh N, Wild PJ, Bode PK et al (2013) Retroperitoneal teratoma with somatic malignant transformation: a papillary renal cell carcinoma in a testicular germ cell tumour metastasis following platinum-based chemotherapy. BMC Urol 13:9
van der Voort R, Taher TE, Derksen PW et al (2000) The hepatocyte growth factor/Met pathway in development, tumorigenesis, and B-cell differentiation. Adv Cancer Res 79:39–90
Uddin S, Hussain AR, Ahmed M et al (2010) Inhibition of c-MET is a potential therapeutic strategy for treatment of diffuse large B-cell lymphoma. Lab Invest 90:1346–1356
Lam BQ, Dai L, Qin Z (2016) The role of HGF/c-MET signaling pathway in lymphoma. J Hematol Oncol 9:135
Bouattour M, Raymond E, Qin S et al (2018) Recent developments of c-Met as a therapeutic target in hepatocellular carcinoma. Hepatology 67:1132–1149
Graveel CR, DeGroot JD, Sigler RE et al (2010) Germline met mutations in mice reveal mutation - and background-associated differences in tumor profiles. PLoS ONE 5(10):e13586
El Bouchtaoui M, Do Cruzeiro M, Leboeuf C et al (2019) A constitutional activating MET mutation makes the genetic link between malignancies and chronic inflammatory diseases. Clin Cancer Res 25:4504–4515
Chen JD, Kearns S, Porter T et al (2001) MET mutation and familial gastric cancer. J Med Genet 38(8):E26
Toledo RA, Qin Y, Cheng ZM et al (2016) Recurrent mutations of chromatin-remodeling genes and kinase receptors in pheochromocytomas and paragangliomas. Clin Cancer Res 22:2301–2310
Whitworth J, Skytte AB, Sunde L et al (2016) Multilocus inherited neoplasia alleles syndrome: a case series and review. JAMA Oncol 2:373–379
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Adlard, J. Multiple primary cancers (renal papillary, lymphoma and teratoma) and hepatic cysts in association with a pathogenic germline mutation in the MET gene. Familial Cancer 20, 81–83 (2021). https://doi.org/10.1007/s10689-020-00196-z
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DOI: https://doi.org/10.1007/s10689-020-00196-z