Genetic Risk Factors in Melanoma Etiopathogenesis and the Role of Genetic Counseling: A Concise Review

Overview

Journal Bosn J Basic Med Sci

Specialty General Medicine

Date 2022 Apr 25

PMID 35465855

Authors

Nikola Serman

Semir Vranic

Mislav Glibo

Ljiljana Serman

Zrinka Bukvic Mokos

Affiliations

Soon will be listed here.

Abstract

Melanoma is a highly aggressive cancer originating from melanocytes. Its etiopathogenesis is strongly related to genetic, epigenetic, and environmental factors. Melanomas encountered in clinical practice are predominantly sporadic, whereas hereditary melanomas account for approximately 10% of the cases. Hereditary melanomas mainly develop due to mutations in the CDKN2A gene, which encodes two tumor suppressor proteins involved in the cell cycle regulation. CDKN2A, along with CDK4, TERT, and POT1 genes, is a high-risk gene for melanoma. Among the genes that carry a moderate risk are MC1R and MITF, whose protein products are involved in melanin synthesis. The environment also contributes to the development of melanoma. Patients at risk of melanoma should be offered genetic counseling to discuss genetic testing options and the importance of skin UV protection, avoidance of sun exposure, and regular preventive dermatological examinations. Although cancer screening cannot prevent the development of the disease, it allows for early diagnosis when the survival rate is the highest.

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References

Wolf Horrell E, Boulanger M, DOrazio J . Melanocortin 1 Receptor: Structure, Function, and Regulation. Front Genet. 2016; 7:95. PMC: 4885833. DOI: 10.3389/fgene.2016.00095. View

Evans D, van Veen E, Byers H, Evans S, Burghel G, Woodward E . High likelihood of actionable pathogenic variant detection in breast cancer genes in women with very early onset breast cancer. J Med Genet. 2021; 59(2):115-121. PMC: 8788257. DOI: 10.1136/jmedgenet-2020-107347. View

Kitagawa M, Higashi H, Jung H, Suzuki-Takahashi I, Ikeda M, Tamai K . The consensus motif for phosphorylation by cyclin D1-Cdk4 is different from that for phosphorylation by cyclin A/E-Cdk2. EMBO J. 1996; 15(24):7060-9. PMC: 452531. View

Zhang W, Wang S, Gu J, Gao Y, Wang Z, Zhang K . Synergistic tumoricidal effect of combined hPD-L1 vaccine and HER2 gene vaccine. Biochem Biophys Res Commun. 2018; 497(1):394-400. DOI: 10.1016/j.bbrc.2018.02.092. View

Meyerson M . Role of telomerase in normal and cancer cells. J Clin Oncol. 2000; 18(13):2626-34. DOI: 10.1200/JCO.2000.18.13.2626. View

Bishop J, Harland M, Randerson-Moor J, Bishop D . Management of familial melanoma. Lancet Oncol. 2007; 8(1):46-54. DOI: 10.1016/S1470-2045(06)71010-5. View

Hemminki K, Srivastava A, Rachakonda S, Bandapalli O, Nagore E, Hemminki A . Informing patients about their mutation tests: CDKN2A c.256G>A in melanoma as an example. Hered Cancer Clin Pract. 2020; 18:15. PMC: 7393828. DOI: 10.1186/s13053-020-00146-x. View

Huang F, Hodis E, Xu M, Kryukov G, Chin L, Garraway L . Highly recurrent TERT promoter mutations in human melanoma. Science. 2013; 339(6122):957-9. PMC: 4423787. DOI: 10.1126/science.1229259. View

Wang F, Luo M, Qu H, Cheng Y . BAP1 promotes viability and migration of ECA109 cells through KLF5/CyclinD1/FGF-BP1. FEBS Open Bio. 2021; 11(5):1497-1503. PMC: 8091813. DOI: 10.1002/2211-5463.13105. View

10.

Soura E, Eliades P, Shannon K, Stratigos A, Tsao H . Hereditary melanoma: Update on syndromes and management: Genetics of familial atypical multiple mole melanoma syndrome. J Am Acad Dermatol. 2016; 74(3):395-407. PMC: 4761105. DOI: 10.1016/j.jaad.2015.08.038. View

11.

Karimian A, Ahmadi Y, Yousefi B . Multiple functions of p21 in cell cycle, apoptosis and transcriptional regulation after DNA damage. DNA Repair (Amst). 2016; 42:63-71. DOI: 10.1016/j.dnarep.2016.04.008. View

12.

Calvete O, Garcia-Pavia P, Dominguez F, Bougeard G, Kunze K, Braeuninger A . The wide spectrum of POT1 gene variants correlates with multiple cancer types. Eur J Hum Genet. 2017; 25(11):1278-1281. PMC: 5643968. DOI: 10.1038/ejhg.2017.134. View

13.

Malumbres M, Barbacid M . Cell cycle, CDKs and cancer: a changing paradigm. Nat Rev Cancer. 2009; 9(3):153-66. DOI: 10.1038/nrc2602. View

14.

Fuiten A, Fankhauser R, Smit D, Stark M, Enright T, Wood M . Genetic analysis of multiple primary melanomas arising within the boundaries of congenital nevi depigmentosa. Pigment Cell Melanoma Res. 2021; 34(6):1123-1130. DOI: 10.1111/pcmr.12979. View

15.

Cabaret O, Perron E, Bressac-de Paillerets B, Soufir N, De la Fouchardiere A . Occurrence of BAP1 germline mutations in cutaneous melanocytic tumors with loss of BAP1-expression: A pilot study. Genes Chromosomes Cancer. 2017; 56(9):691-694. DOI: 10.1002/gcc.22473. View

16.

Taylor N, Mitra N, Qian L, Avril M, Bishop D, Bressac-de Paillerets B . Estimating CDKN2A mutation carrier probability among global familial melanoma cases using GenoMELPREDICT. J Am Acad Dermatol. 2019; 81(2):386-394. PMC: 6634996. DOI: 10.1016/j.jaad.2019.01.079. View

17.

Trigueros-Motos L . Mutations in POT1 predispose to familial cutaneous malignant melanoma. Clin Genet. 2014; 86(3):217-8. DOI: 10.1111/cge.12416. View

18.

Weber H, Samuel T, Rauch P, Funk J . Human p14(ARF)-mediated cell cycle arrest strictly depends on intact p53 signaling pathways. Oncogene. 2002; 21(20):3207-12. DOI: 10.1038/sj.onc.1205429. View

19.

Lee G, Kunitake H, Stafford C, Bordeianou L, Francone T, Ricciardi R . High Risk of Proximal and Local Neoplasms in 2206 Patients With Anogenital Extramammary Paget's Disease. Dis Colon Rectum. 2019; 62(11):1283-1293. PMC: 6785398. DOI: 10.1097/DCR.0000000000001487. View

20.

Morani A, Hanafy A, Ramani N, Katabathina V, Yedururi S, Dasyam A . Hereditary and Sporadic Pancreatic Ductal Adenocarcinoma: Current Update on Genetics and Imaging. Radiol Imaging Cancer. 2021; 2(2):e190020. PMC: 7983791. DOI: 10.1148/rycan.2020190020. View