Marker Genes of Clear Cell Renal Cell Carcinoma
DOI:
https://doi.org/10.12775/JEHS.2024.62.52911Keywords
clear cell renal cell carcinoma, marker genesAbstract
An analysis was conducted on marker genes indicating the induction of clear cell renal cell carcinoma (ccRCC) and their role in the pathogenesis of this oncological disease.
The diagnostic and therapeutic approaches for ccRCC are evolving with the identification of marker genes. The use of molecular biology methods has enabled the detection of somatic mutations in RCC marker genes like VHL, BAP1, OGG1, FLCN, MDM2, TP53, and RNF139. Targeted drugs like sorafenib, sunitinib, bevacizumab, pazopanib, axitinib, everolimus, and temsirolimus are being utilized in the treatment of RCC metastases. The diagnostic value of specific alleles in marker genes like rs1642742 and rs779805 of the VHL gene, rs1052133 of the OGG1 gene, rs2279744 of the MDM2 gene, and rs1597368777 of the TP53 gene has been confirmed in detecting ccRCC. Mutations in these marker genes play a significant role in the pathogenesis of ccRCC and are associated with the development and progression of the disease.
The identification of these mutations can aid in the diagnosis, prognosis, and treatment of ccRCC.
Marker genes are essential in understanding the molecular mechanisms underlying ccRCC. Mutations in genes like VHL, BAP1, OGG1, FLCN, MDM2, TP53, and RNF139 are key drivers of ccRCC pathogenesis. The diagnostic and therapeutic implications of these mutations are significant in the management of ccRCC. Further research into the role of marker genes in ccRCC is essential for developing targeted therapies and improving patient outcomes.
References
Arai E., Kanai Y. Genetic and epigenetic alterations during renal carcinogenesis//Int J Clin Exp Pathol.-2011.-Т.4,№1.-С.58-73
Audebert M., Chevillard S., Levalois C. et al. Alterations of the DNA Repair Gene OGG1 in Human Clear Cell Carcinomas of the Kidney//Cancer Res.-2000.-Т.60,№17.-С.4740–4744
Ball M.W., An J.Y., Gomella P.T. et al. Growth Rates of Genetically Defined Renal Tumors: Implications for Active Surveillance and Intervention//J Clin Oncol.-2020.-Т.38,№11.-С.1146–1153
doi: 10.1200/JCO.19.02263
Bandoh N., Kubota A., Takeda R. et al., Renal Cell Carcinoma Metastasizing to the Cricoid Cartilage Presenting With Subglottic Stenosis: A Case Report and Literature Review// Ear Nose Throat J.-2023 May 26;1455613231177188
doi: 10.1177/01455613231177188
Bartnykaitė A., Savukaitytė A., Ugenskienė R. et al. Associations of MDM2 and MDM4 Polymorphisms with Early-Stage Breast Cancer//J Clin Med.-2021.-Т.10.№4.-С.866
doi: 10.3390/jcm10040866
Battaglia A. The Importance of Multidisciplinary Approach in Early Detection of BAP1 Tumor Predisposition Syndrome: Clinical Management and Risk Assessment//Clin Med Insights Oncol.-2014.-Т.8.-С.37–47
doi: 10.4137/CMO.S15239
Bell H.N., Kumar-Sinha C., Mannan R. et al. Pathogenic ATM and BAP1 germline mutations in a case of early-onset, familial sarcomatoid renal cancer// Cold Spring Harb Mol Case Stud.-2022.-Т.8,№3.-С.a006203
doi: 10.1101/mcs.a006203
Cancer Genome Atlas Research Network. Comprehensive molecular characterization of clear cell renal cell carcinoma. The //Nature.-2013.-Т.499,№7456.-С.43–49
doi:10.1038/nature12222
Chang W.-S., Shen T.-S., Liao J.-M. et al. Significant Contribution of DNA Repair Human 8-Oxoguanine DNA N-Glycosylase 1 Genotypes to Renal Cell Carcinoma//Onco Targets Ther.-2020.-Т.13.-С.1583-1591
doi: 10.2147/OTT.S231733
Chen X., Zhang H., Ou S., Chen H. Von Hippel-Lindau gene single nucleotide polymorphism (rs1642742) may be related to the occurrence and metastasis of HBV-related hepatocellular carcinoma//Medicine (Baltimore).-2021.-Т.100,№35.-С.e27187
doi: 10.1097/MD.0000000000027187
Chrabańska M., Szweda-Gandor N., Drozdzowska B. Two Single Nucleotide Polymorphisms in the Von Hippel-Lindau Tumor Suppressor Gene in Patients with Clear Cell Renal Cell Carcinoma// Int J Mol Sci.-2023.-Т.24,№4.-С.3778
doi: 10.3390/ijms24043778
Collins A.R., Gaivão I. DNA base excision repair as a biomarker in molecular epidemiology studies//Mol Aspects Med.-2007.-Т.28,№3-4.-С.307-322
doi: 10.1016/j.mam.2007.05.005
Courtney K.D., Ma Y., Diaz de Leon A. et al. HIF-2 Complex Dissociation, Target Inhibition, and Acquired Resistance with PT2385, a First-in-Class HIF-2 Inhibitor in Clear Cell Renal Cell Carcinoma Patients//Clin Cancer Res.-2020.-Т.26,№4.-С.793–803
doi: 10.1158/1078-0432.CCR-19-1459
Daccord C., Good J.-M., Morren M.-A. et al. Birt–Hogg–Dubé syndrome//Eur Respir Rev.-2020.-Т.29,вып.157.-С.200042
doi: 10.1183/16000617.0042-2020
Dell’Atti L., Bianchi N., Aguiar G. New Therapeutic Interventions for Kidney Carcinoma: Looking to the Future//Cancers (Basel).-2022.-Т.14,№15.-С.3616
doi: 10.3390/cancers14153616
Diesing K., Ribback S., Winter S. et al. p53 is functionally inhibited in clear cell renal cell carcinoma (ccRCC): a mechanistic and correlative investigation into genetic and molecular characteristics//J Cancer Res Clin Oncol.-2021.-Т.147,№12.-С.3565–3576
doi: 10.1007/s00432-021-03786-1
Diez-Calzadilla N.A., Noguera Salvá R., Soriano Sarrió P., Martínez-Jabaloyas J. M. Genetic profile and immunohistochemical study of clear cell renal carcinoma: Pathological-anatomical correlation and prognosis//Cancer Treat Res Commun.-2021.-Т.27.-С.100374
doi: 10.1016/j.ctarc.2021.100374
Farley M.N., Schmidt L.S., Mester J.L. et al. A Novel Germline Mutation in BAP1 Predisposes to Familial Clear-Cell Renal Cell Carcinoma//Mol Cancer Res.-2013.-Т.11,№9.-С.1061–1071
doi: 10.1158/1541-7786.MCR-13-0111
Furuya M., Hong S.-B., Tanaka R. et al. Distinctive expression patterns of glycoprotein non-metastatic B and folliculin in renal tumors in patients with Birt–Hogg–Dubé syndrome//Cancer Sci.-2015.-Т.106,№3.-С.315–323
doi: 10.1111/cas.12601
Gemmill R.M., West J.D., Boldog F. et al. The hereditary renal cell carcinoma 3;8 translocation fuses FHIT to a patched-related gene, TRC8// Proc Natl Acad Sci U S A.-1998.- Т.95,№16.-С.9572–9577
doi: 10.1073/pnas.95.16.9572
Gilyazova I.R., Beeraka N.M., Klimentova E.A. et al. Novel MicroRNA Binding Site SNPs and the Risk of Clear Cell Renal Cell Carcinoma (ccRCC): A Case-Control Study// Curr Cancer Drug Targets.-2020
doi: 10.2174/1568009620666201120151226
Gimelli S., Beri S., Drabkin H.A. et al. The tumor suppressor gene TRC8/RNF139 is disrupted by a constitutional balanced translocation t(8;22)(q24.13;q11.21) in a young girl with dysgerminoma//Mol Cancer.-2009.-Т.8.-С.52
doi: 10.1186/1476-4598-8-52
Habib S.L. Insight into mechanism of oxidative DNA damage in angiomyolipomas from TSC patients//Mol Cancer.-2009.-Т.8.-С.13
doi: 10.1186/1476-4598-8-13
Hirata H., Hinoda Y., Kikuno N. et al., MDM2 SNP309 Polymorphism as Risk Factor for Susceptibility and Poor Prognosis in Renal Cell Carcinoma Clin Cancer Res.-2007.-Т.13,№14.-С.4123-4129
doi: 10.1158/1078-0432.CCR-07-0609
Hsieh J.J. et al. Renal cell carcinoma//Nat Rev Dis Primers.-2018.-Т.3.-С.17009 doi:10.1038/nrdp.2017.9
Kato T., Franconi C.P., Sheridan M.B. et al. Analysis of the t(3;8) of Hereditary Renal Cell Carcinoma: A Palindrome-Mediated Translocation//Cancer Genet.-2014.-Т.207,№4.-С.133–140
doi: 10.1016/j.cancergen.2014.03.004
Kuroda N., Furuya M., Nagashima Y. et al. Review of renal tumors associated with Birt-Hogg-Dubé syndrome with focus on clinical and pathobiological aspects//Pol J Pathol.-2014.-Т.65,№2.-С.93-99
doi: https://doi.org/10.5114/pjp.2014.43958
Lalonde M.-E., Ouimet M., Larivière M. et al. Identification of functional DNA variants in the constitutive promoter region of MDM2//Hum Genomics.-2012.-Т.6,№1.-С.15
doi: 10.1186/1479-7364-6-15
Li F., Aljahdali I.A.M., Zhang R. et al. Kidney cancer biomarkers and targets for therapeutics: survivin (BIRC5), XIAP, MCL-1, HIF1α, HIF2α, NRF2, MDM2, MDM4, p53, KRAS and AKT in renal cell carcinomaJournal of Experimental & Clinical Cancer Research.-2021.-Т.40.-С.254
doi.org/10.1186/s13046-021-02026-1
Liu K., Xu W., Tian X. et al. Genotypic characteristics of Chinese patients with BHD syndrome and functional analysis of FLCN variants//Orphanet J Rare Dis.-2019.-Т.14,№1.-С.223
doi: 10.1186/s13023-019-1198-y
Liu Y., Xu Z., Feng R. et al. Clinical and genetic characteristics of chinese patients with Birt-Hogg-Dubé syndrome//Orphanet J Rare Dis.-2017.-Т.12.-С.104
doi: 10.1186/s13023-017-0656-7
Maher E.R. Hereditary renal cell carcinoma syndromes: diagnosis, surveillance and management//World J Urol.-2018.-Т.36,№12.-С.1891–1898
doi: 10.1007/s00345-018-2288-5
Mahmoud A.A., Hassan M.H., Ghweil A.A. et al. Urinary 8-hydroxydeoxyguanosine in relation to XRCC1 rs25487 G/A (Arg399Gln) and OGG1 rs1052133 C/G (Ser326Cys) DNA repair genes polymorphisms in patients with chronic hepatitis C and related hepatocellular carcinoma//Cancer Manag Res.-2019.-Т.11.-С.5343-5351
doi: 10.2147/CMAR.S209112
Moch H., Amin M.B., Berney D.M. et al., The 2022 World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs—Part A: Renal, Penile, and Testicular Tumours Eur Urol (2022), https://doi.org/10.1016/j.eururo.2022.06.016
Moch H. et al., The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs—Part A: Renal, Penile, and Testicular
Tumours European urology.-2016.-T.70.-C.93 – 105
doi.org/10.1016/j.eururo.2016.02.029
Moore L.E., Nickerson M.L., Brennan P. et al. Von Hippel-Lindau (VHL) Inactivation in Sporadic Clear Cell Renal Cancer: Associations with Germline VHL Polymorphisms and Etiologic Risk Factors//PLoS Genet.-2011.-Т.7,№10.-С.e1002312
doi: 10.1371/journal.pgen.1002312
Nilsson H., Lindgren D., Axelson H. et al. Features of increased malignancy in eosinophilic clear cell renal cell carcinoma//J Pathol.-2020.-Т.252,№4.-С.384–397
doi: 10.1002/path.5532
Noon A.P., Vlatković N., Polański R. et al. p53 and MDM2 in Renal Cell Carcinoma//Cancer.-2010.-Т.116,№4.-С.780–790
doi: 10.1002/cncr.24841
Nordstrom-O’Brien M., van der Luijt R.B., van Rooijen E. et al. Genetic Analysis of von Hippel-Lindau Disease//Human mutation.-2010.-Т.31,№5.С.521 – 537
Okimoto K., Sakurai J., Kobayashi T. et al. A germ-line insertion in the Birt–Hogg–Dube ́(BHD)gene gives rise to the Nihon rat model of inheritedrenal cancer//PNAS.-2004.-Т.101,№7.-С.2023–2027
doi.org/10.1073/pnas.0308071100
Olfson E., Cottrell C.E., Davidson N.O. et al. Identification of Medically Actionable Secondary Findings in the 1000 Genomes//PLoS One.-2015.-Т.10.№9.-С. e0135193
doi: 10.1371/journal.pone.0135193
Patard J.-J., Fergelot P., Karakiewicz P.I. et al. Low CAIX expression and absence of VHL gene mutation are associated with tumor aggressiveness and poor survival of clear cell renal cell carcinoma// Int J Cancer.-2008.-Т.123,№2.-С.395–400
doi: 10.1002/ijc.23496
Peña-Llopis S., Vega-Rubín-de-Celis S., Liao A. et al. BAP1 loss defines a new class of renal cell carcinoma//Nature Genetics.-2012.-Т.44,№7.-С.751–759
doi: 10.1038/ng.2323
Popova T., Hebert L., Jacquemin V. et al. Germline BAP1 mutations predispose to renal cell carcinomas//Am J Hum Genet.-2013.-Т.92,№6.-С.974-980
doi: 10.1016/j.ajhg.2013.04.012
Qin C., Cao Q., Ju X. et al. The polymorphisms in the VHL and HIF1A genes are
associated with the prognosis but not the development of renal cell carcinoma//Annals of Oncology.-2012.-Т.23.-С.981–989
doi:10.1093/annonc/mdr325
Remenyi G., Bereczky Z., Gindele R. et al. rs779805 Von Hippel-Lindau Gene Polymorphism Induced/Related Polycythemia Entity, Clinical Features, Cancer Association, and Familiar Characteristics//Pathol Oncol Res.-2021.-27.-С.1609987
doi: 10.3389/pore.2021.1609987
Schmidt L.S., Nickerson M.L., Warren M.B. et al. Germline BHD-Mutation Spectrum and Phenotype Analysis of a Large Cohort of Families with Birt-Hogg-Dubé Syndrome//Am J Hum Genet.-2005.-Т.76,№6.—С.1023–1033
doi: 10.1086/430842
Schmidt L.S., Linehan W.M. FLCN: the causative gene for Birt-Hogg-Dubé syndrome// Gene.-2018.-Т.640.-С.28–42
doi: 10.1016/j.gene.2017.09.044
Szegedi K., Szabó Z., Kállai J. et al. Potential Role of VHL, PTEN, and BAP1 Mutations in Renal Tumors//J Clin Med.-2023.-Т.12,№13.-С.4538
doi: 10.3390/jcm12134538
Shi B., Ding J., Qi J., Gu Z. Characteristics and prognostic value of potential dependency genes in clear cell renal cell carcinoma based on a large-scale CRISPR-Cas9 and RNAi screening database DepMap//Int J Med Sci.-2021.-Т.18,№9.-С.2063-2075
doi: 10.7150/ijms.51703
Testa U., Pelosi E., Castelli G. Genetic Alterations in Renal Cancers: Identification of The Mechanisms Underlying Cancer Initiation and Progression and of Therapeutic Targets//Medicines (Basel).-2020.-Т.7,№8.-С.44
doi: 10.3390/medicines7080044
Tsai C.-W., Tsai M.-H., Tsou Y.-A. et al. The joint effect of smoking and hOGG1 genotype on oral cancer in Taiwan//Anticancer Res.-2012.-Т.32,№9.-С.3799-3803
Uhlman D.L., Nguyen P.L., Manivel J.C. et al., Association of immunohistochemical staining for p53 with metastatic progression and poor survival in patients with renal cell carcinoma//J Natl Cancer Inst.-1994.-Т.86,№19.-С.1470-1475
doi: 10.1093/jnci/86.19.1470
Verbiest A., Lambrechts D., Van Brussel T. et al. Polymorphisms in the Von Hippel-Lindau Gene Are Associated With Overall Survival in Metastatic Clear-Cell Renal-Cell Carcinoma Patients Treated With VEGFR Tyrosine Kinase Inhibitors//Clin Genitourin Cancer.-2018.-Т.16,№4.-С.266-273
doi: 10.1016/j.clgc.2018.01.013
Wang W.-C., Tsou M.-H., Chen H.-J. et al. Two single nucleotide polymorphisms in the von Hippel-Lindau tumor suppressor gene in Taiwanese with renal cell carcinoma//BMC Res Notes.-2014.-Т.7.-С.638
doi: 10.1186/1756-0500-7-638
Warren A.Y., Harrison D. WHO/ISUP classification, grading and pathological staging of renal cell carcinoma: standards and controversies//World Journal of Urology.-2018.-T.36.-C.1913–1926
doi.org/10.1007/s00345-018-2447-8
Weaver C., Bin Satter K., Richardson K.P. et al. Diagnostic and Prognostic Biomarkers in Renal Clear Cell Carcinoma// Biomedicines.-2022.-Т.10,№11.-С.2953
doi: 10.3390/biomedicines10112953
Williamson S.R., Gill A.J., Argani et al. Report From the International Society of Urological Pathology (ISUP) Consultation Conference on Molecular Pathology of Urogenital Cancers: III: Molecular Pathology of Kidney Cancer// Am J Surg Pathol.-2020.-Т.44,№7.-С.e47-e65
doi: 10.1097/PAS.0000000000001476
Yamane A., Kohno T., Ito K. et al. Differential ability of polymorphic OGG1 proteins to suppress mutagenesis induced by 8-hydroxyguanine in human cell in vivo//Carcinogenesis.-2004.-Т.25,№9.-С.1689-1694
doi: 10.1093/carcin/bgh166
Yu M., Zhang Q., Zhao X. Associations of MDM2 rs2279744 and TP53 rs1042522 polymorphisms with cervical cancer risk: A meta-analysis and systematic review//Front Oncol.-2022.-Т.12.-С.973077
doi: 10.3389/fonc.2022.973077
Zhang C., Ye Z., Zhang Z. et al. A comprehensive evaluation of single nucleotide polymorphisms associated with hepatocellular carcinoma risk in Asian populations: A systematic review and network meta-analysis//Gene.-2020.-Т.735.-С.144365
doi: 10.1016/j.gene.2020.144365
Zhao H., Qin C., Yan F. et al. hOGG1 Ser326Cys polymorphism and renal cell carcinoma risk in a Chinese population// DNA Cell Biol.-2011.-Т.30,№5.-С.317-321
doi: 10.1089/dna.2010.1135
Zhao X., Ma Y., Cui J. et al. FLCN Regulates HIF2α Nuclear Import and Proliferation of Clear Cell Renal Cell Carcinoma//Front Mol Biosci.-2020.-Т.7.-С.121
doi: 10.3389/fmolb.2020.00121
Downloads
Published
How to Cite
Issue
Section
License
Copyright (c) 2024 Sergey Dolomatov, Walery Zukow
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The periodical offers access to content in the Open Access system under the Creative Commons Attribution-NonCommercial-ShareAlike 4.0
Stats
Number of views and downloads: 325
Number of citations: 0
