Patients with Papillary Renal Cancer and Germline Duplication of <i>MET</i> Exons 5-21
Hereditary papillary renal carcinoma (HPRC) is a rare monogenic hereditary disease in the group of hereditary cancer syndromes. Clinically, HPRC results in the development of multiple papillary renal cell carcinomas of the kidneys in young adults. HPRC is caused by point activating mutations in the...
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2025-05-01
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| author | Dmitry S. Mikhaylenko Natalya B. Kuryakova Fatima M. Bostanova Viktoria V. Zabnenkova Oksana P. Ryzhkova Ilya V. Volodin Dmitry V. Zaletaev Dmitry V. Pustoshilov Sergey I. Kutsev Vladimir V. Strelnikov |
| author_facet | Dmitry S. Mikhaylenko Natalya B. Kuryakova Fatima M. Bostanova Viktoria V. Zabnenkova Oksana P. Ryzhkova Ilya V. Volodin Dmitry V. Zaletaev Dmitry V. Pustoshilov Sergey I. Kutsev Vladimir V. Strelnikov |
| author_sort | Dmitry S. Mikhaylenko |
| collection | DOAJ |
| description | Hereditary papillary renal carcinoma (HPRC) is a rare monogenic hereditary disease in the group of hereditary cancer syndromes. Clinically, HPRC results in the development of multiple papillary renal cell carcinomas of the kidneys in young adults. HPRC is caused by point activating mutations in the <i>MET</i> gene encoding a transmembrane tyrosine kinase receptor. Until now, all detected germline mutations in HPRC patients were missense variants leading to a constitutive activation of the tyrosine kinase domain. We describe, for the first time, unrelated patients with clinical features similar to HPRC and without <i>MET</i> pathogenic missense variants but harboring an extended heterozygous duplication ~101.4 kb in length (chr7:116740252-116841718) in 7q31.2 determined using whole-genome sequencing (WGS). This duplication results in an additional copy of the <i>MET</i> gene fragment, including exons 5-21. The duplicated exons encode most of the receptor domains. According to the American College of Medical Genetics and Genomics (ACMG) criteria, this duplication is classified as variant of uncertain significance (VUS) at present, but it is not excluded that this duplication may represent an activating mutation. Perhaps, further segregation analysis and functional studies will allow us to more accurately resolve the pathogenicity and diagnostic significance of this germline CNV. |
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| institution | Kabale University |
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| language | English |
| publishDate | 2025-05-01 |
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| series | Biomedicines |
| spelling | doaj-art-c7dfe5fc4dcb462999bc44ac0fe02f672025-08-20T03:27:15ZengMDPI AGBiomedicines2227-90592025-05-01136132910.3390/biomedicines13061329Patients with Papillary Renal Cancer and Germline Duplication of <i>MET</i> Exons 5-21Dmitry S. Mikhaylenko0Natalya B. Kuryakova1Fatima M. Bostanova2Viktoria V. Zabnenkova3Oksana P. Ryzhkova4Ilya V. Volodin5Dmitry V. Zaletaev6Dmitry V. Pustoshilov7Sergey I. Kutsev8Vladimir V. Strelnikov9Research Centre for Medical Genetics, Moskvorechie st., 1, 115522 Moscow, RussiaResearch Centre for Medical Genetics, Moskvorechie st., 1, 115522 Moscow, RussiaResearch Centre for Medical Genetics, Moskvorechie st., 1, 115522 Moscow, RussiaResearch Centre for Medical Genetics, Moskvorechie st., 1, 115522 Moscow, RussiaResearch Centre for Medical Genetics, Moskvorechie st., 1, 115522 Moscow, RussiaResearch Centre for Medical Genetics, Moskvorechie st., 1, 115522 Moscow, RussiaResearch Centre for Medical Genetics, Moskvorechie st., 1, 115522 Moscow, Russia“Biotech Campus” LLC., Mikluho-Maklaya st., 117437 Moscow, RussiaResearch Centre for Medical Genetics, Moskvorechie st., 1, 115522 Moscow, RussiaResearch Centre for Medical Genetics, Moskvorechie st., 1, 115522 Moscow, RussiaHereditary papillary renal carcinoma (HPRC) is a rare monogenic hereditary disease in the group of hereditary cancer syndromes. Clinically, HPRC results in the development of multiple papillary renal cell carcinomas of the kidneys in young adults. HPRC is caused by point activating mutations in the <i>MET</i> gene encoding a transmembrane tyrosine kinase receptor. Until now, all detected germline mutations in HPRC patients were missense variants leading to a constitutive activation of the tyrosine kinase domain. We describe, for the first time, unrelated patients with clinical features similar to HPRC and without <i>MET</i> pathogenic missense variants but harboring an extended heterozygous duplication ~101.4 kb in length (chr7:116740252-116841718) in 7q31.2 determined using whole-genome sequencing (WGS). This duplication results in an additional copy of the <i>MET</i> gene fragment, including exons 5-21. The duplicated exons encode most of the receptor domains. According to the American College of Medical Genetics and Genomics (ACMG) criteria, this duplication is classified as variant of uncertain significance (VUS) at present, but it is not excluded that this duplication may represent an activating mutation. Perhaps, further segregation analysis and functional studies will allow us to more accurately resolve the pathogenicity and diagnostic significance of this germline CNV.https://www.mdpi.com/2227-9059/13/6/1329hereditary papillary renal cancergene <i>MET</i>germline duplicationnext generation sequencing |
| spellingShingle | Dmitry S. Mikhaylenko Natalya B. Kuryakova Fatima M. Bostanova Viktoria V. Zabnenkova Oksana P. Ryzhkova Ilya V. Volodin Dmitry V. Zaletaev Dmitry V. Pustoshilov Sergey I. Kutsev Vladimir V. Strelnikov Patients with Papillary Renal Cancer and Germline Duplication of <i>MET</i> Exons 5-21 Biomedicines hereditary papillary renal cancer gene <i>MET</i> germline duplication next generation sequencing |
| title | Patients with Papillary Renal Cancer and Germline Duplication of <i>MET</i> Exons 5-21 |
| title_full | Patients with Papillary Renal Cancer and Germline Duplication of <i>MET</i> Exons 5-21 |
| title_fullStr | Patients with Papillary Renal Cancer and Germline Duplication of <i>MET</i> Exons 5-21 |
| title_full_unstemmed | Patients with Papillary Renal Cancer and Germline Duplication of <i>MET</i> Exons 5-21 |
| title_short | Patients with Papillary Renal Cancer and Germline Duplication of <i>MET</i> Exons 5-21 |
| title_sort | patients with papillary renal cancer and germline duplication of i met i exons 5 21 |
| topic | hereditary papillary renal cancer gene <i>MET</i> germline duplication next generation sequencing |
| url | https://www.mdpi.com/2227-9059/13/6/1329 |
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