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Diagnostics of hereditary cancer syndromes with papillary renal tumors
https://doi.org/10.25557/2073-7998.2026.07.47-57
Abstract
Background. Papillary renal cancer (PRC) is the second most common malignant renal neoplasm. Rare hereditary forms of PRC are presented by several monogenic diseases with partially overlapping phenotypes. Therefore, improving the effectiveness of molecular genetic diagnostics and medical genetic counseling for hereditary PRC is an actual problem.
Methods. We have analyzed 32 genomic DNA samples from patients with hereditary papillary renal cell carcinoma (HPRC) and hereditary leiomyomatosis and renal cell carcinoma (HLRCC) syndromes using sequencing and multiplex ligase-dependent probe amplification.
Results and discussion. Point pathogenic/likely pathogenic variants were identified in 5 families. The c.3274G>A (MET) and c.395_399del (FH) variants previously not described as common mutations, although we have detected those variants in two or more probands from different families in our cohort. Duplication of exons 5-21 of the MET gene was detected in 21% of HPRC cases. This duplication is currently of uncertain clinical significance, but in silico predictors indicate its pathogenicity. Also, we propose management of mutation carriers and an improved diagnostic protocol for hereditary PRC in accordance with international consensus.
Conclusions. Diagnosis of hereditary PRC requires analysis of both point mutations and copy number of the MET and FH genes considering the tumor type.
Supporting agencies: This study was supported by the Ministry of Science and Higher Education of the Russian Federation (as part of the Federal Scientific and Technical Program for the Development of Genetic Technologies for 2019–2030, Agreement No. 075-15-2025-481).
About the Authors
D. S. Mikhaylenko
Research Centre for Medical Genetics; I.M. Sechenov First Moscow State Medical University (Sechenov University)
Russian Federation
Russian Federation
1 Moskvorechie str., Moscow, 115522
8/2 Trubetskaya str., Moscow, 119048
N. B. Kuryakova
Research Centre for Medical Genetics
Russian Federation
Russian Federation
1 Moskvorechie str., Moscow, 115522
O. A. Solovova
Research Centre for Medical Genetics
Russian Federation
Russian Federation
1 Moskvorechie str., Moscow, 115522
A. V. Efremova
Research Centre for Medical Genetics
Russian Federation
Russian Federation
1 Moskvorechie str., Moscow, 115522
N. A. Gorban
Research Centre for Medical Genetics; A.F. Tsyb MRRC– branch of the National Medical Research Center of Radiology
Russian Federation
Russian Federation
1 Moskvorechie str., Moscow, 115522
4 Koroleva str., Obninsk, 249036
V. V. Strelnikov
Research Centre for Medical Genetics
Russian Federation
Russian Federation
1 Moskvorechie str., Moscow, 115522
D. V. Zaletayev
Research Centre for Medical Genetics
Russian Federation
Russian Federation
1 Moskvorechie str., Moscow, 115522
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For citations:
Mikhaylenko D.S., Kuryakova N.B., Solovova O.A., Efremova A.V., Gorban N.A., Strelnikov V.V., Zaletayev D.V. Diagnostics of hereditary cancer syndromes with papillary renal tumors. Medical Genetics. 2026;25(7):47-57. (In Russ.) https://doi.org/10.25557/2073-7998.2026.07.47-57
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