Genetic profiling of a rare condition: co-occurrence of albinism and multiple primary melanoma in a Caucasian family
- PMID: 27776349
- PMCID: PMC5444700
- DOI: 10.18632/oncotarget.12777
Genetic profiling of a rare condition: co-occurrence of albinism and multiple primary melanoma in a Caucasian family
Abstract
Multiple primary melanoma (MPM) is a rare condition, whose genetic basis has not yet been clarified. Only 8-12% of MPM are due to germline mutations of CDKN2A. However, other genes (POT1, BRCA1/2, MC1R, MGMT) have been demonstrated to be involved in predisposition to this pathology.To our knowledge, this is the first family study based on two siblings with the rare coexistence of MPM and oculocutaneous albinism (OCA), an autosomal recessive disease characterized by the absence or decrease in pigmentation in the skin, hair, and eyes.In this study, we evaluated genes involved in melanoma predisposition (CDKN2A, CDK4, MC1R, MITF, POT1, RB1, MGMT, BRCA1, BRCA2), pathogenesis (BRAF, NRAS, PIK3CA, KIT, PTEN), skin/hair pigmentation (MC1R, MITF) and in immune pathways (CTLA4) to individuate alterations able to explain the rare onset of MPM and OCA in indexes and the transmission in their pedigree.From the analysis of the pedigree, we were able to identify a "protective" haplotype with respect to MPM, including MGMT p.I174V alteration. The second generation offspring is under strict follow up as some of them have a higher risk of developing MPM according to our model.
Keywords: MGMT; albinism; family study; multiple primary melanoma; susceptibility.
Figures
Similar articles
-
Germline and somatic mutations in patients with multiple primary melanomas: a next generation sequencing study.BMC Cancer. 2019 Aug 5;19(1):772. doi: 10.1186/s12885-019-5984-7. BMC Cancer. 2019. PMID: 31382929 Free PMC article.
-
Sporadic multiple primary melanoma cases: CDKN2A germline mutations with a founder effect.Genes Chromosomes Cancer. 2001 Nov;32(3):195-202. doi: 10.1002/gcc.1183. Genes Chromosomes Cancer. 2001. PMID: 11579459
-
Cancer risks and survival in patients with multiple primary melanomas: Association with family history of melanoma and germline CDKN2A mutation status.J Am Acad Dermatol. 2017 Nov;77(5):893-901. doi: 10.1016/j.jaad.2017.05.050. Epub 2017 Aug 14. J Am Acad Dermatol. 2017. PMID: 28818438
-
Melanoma genetics.J Med Genet. 2016 Jan;53(1):1-14. doi: 10.1136/jmedgenet-2015-103150. Epub 2015 Sep 3. J Med Genet. 2016. PMID: 26337759 Review.
-
Genetic risk factors in melanoma etiopathogenesis and the role of genetic counseling: A concise review.Bosn J Basic Med Sci. 2022 Sep 16;22(5):673-682. doi: 10.17305/bjbms.2021.7378. Bosn J Basic Med Sci. 2022. PMID: 35465855 Free PMC article. Review.
Cited by
-
Multigene panel sequencing of established and candidate melanoma susceptibility genes in a large cohort of Dutch non-CDKN2A/CDK4 melanoma families.Int J Cancer. 2019 May 15;144(10):2453-2464. doi: 10.1002/ijc.31984. Epub 2019 Jan 21. Int J Cancer. 2019. PMID: 30414346 Free PMC article.
-
Characterizing melanoma in the setting of oculocutaneous albinism: an analysis of the literature.Arch Dermatol Res. 2023 Oct;315(8):2413-2417. doi: 10.1007/s00403-022-02364-w. Epub 2022 Jul 18. Arch Dermatol Res. 2023. PMID: 35849167
-
Genetic Variants and Somatic Alterations Associated with MITF-E318K Germline Mutation in Melanoma Patients.Genes (Basel). 2021 Sep 18;12(9):1440. doi: 10.3390/genes12091440. Genes (Basel). 2021. PMID: 34573422 Free PMC article.
-
The Genetic Germline Background of Single and Multiple Primary Melanomas.Front Mol Biosci. 2021 Mar 5;7:555630. doi: 10.3389/fmolb.2020.555630. eCollection 2020. Front Mol Biosci. 2021. PMID: 33748184 Free PMC article.
-
Melanoma susceptibility: an update on genetic and epigenetic findings.Int J Mol Epidemiol Genet. 2021 Oct 15;12(5):71-89. eCollection 2021. Int J Mol Epidemiol Genet. 2021. PMID: 34853632 Free PMC article. Review.
References
-
- Buljan M, Situm M, Bolanca Z, Zivkovic MV, Mihic LL. Multiple primary melanoma: epidemiological and prognostic implications; analysis of 36 cases. Coll Antropol. 2010;34(2):131–4. - PubMed
-
- De Giorgi V, Savarese I, D’Errico A, Gori A, Papi F, Colombino M, Sini MC, Stanganelli I, Palmieri G, Massi D. CDKN2A mutations could influence the dermoscopic pattern of presentation of multiple primary melanoma: a clinical dermoscopic genetic study. J Eur Acad Dermatol Venereol. 2015;29:574–80. doi: 10.1111/jdv.12643. - DOI - PubMed
-
- Puig S, Malvehy J, Badenas C, Ruiz A, Jimenez D, Cuellar F, Azon A, Gonzalez U, Castel T, Campoy A, Herrero J, Marti R, Brunet-Vidal J, et al. Role of the CDKN2A locus in patients with multiple primary melanomas. J Clin Oncol. 2005;23:3043–51. doi: 10.1200/JCO.2005.08.034. 23/13/3043. - DOI - PubMed
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Research Materials
Miscellaneous