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CDKN2A mutations and MC1R variants in Italian patients with single or multiple primary melanoma.
Pigment Cell Melanoma Res 2008; 21(6):700-9PC

Abstract

We evaluated the contribution of germline CDKN2A mutations and MC1R variants to the development of melanoma in a hospital-based study of single (SPM, n = 398) and multiple primary melanoma (MPM, n = 95). The overall frequency of CDKN2A mutations was 15.2%, and four-fold higher in MPM than in SPM cases (OR = 4.27; 95% CI 2.43-7.53). The likelihood of identifying a CDKN2A mutation increased with family history of melanoma and younger age at diagnosis in MPM cases. Compared to SPM patients, the risk of harboring a CDKN2A mutation rose as the number of primary melanomas increased and was not influenced by family history. The G101W and E27X founder mutations were the most common. Several other mutations (W15X, Q50X, R58X, A68L, A127P and H142R) were detected for the first time in Italian patients. One novel mutation, T77A, was identified. Several non-coding variants with unknown functional significance were also found (5'UTR -25C > T, -21C > T, -67G > C, IVS1 +37G > C); the novel 5'UTR -21C > T variant was not detected in controls. The CDKN2A A148T polymorphism was more frequent in MPM patients than in the control population (15.7% versus 6.6%). Compared to the SPM patients, MPM cases had a 2-fold increased probability of being MC1R variant carriers and a higher probability of carrying two or more variants. No specific association was observed between the type of variant and the number of melanomas, suggesting that the number rather than the type of MC1R variant increases the risk of MPM. We observed no interaction between CDKN2A status and the presence of MC1R variants. The high frequency of CDKN2A mutations in our MPM cases, independent of their family history, is of relevance to genetic counseling and testing in our population.

Authors+Show Affiliations

Department of Oncology, Biology and Genetics/Medical Genetics Service, University of Genoa, Genoa, Italy. l.pastorino@unige.itNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18983535

Citation

Pastorino, L, et al. "CDKN2A Mutations and MC1R Variants in Italian Patients With Single or Multiple Primary Melanoma." Pigment Cell & Melanoma Research, vol. 21, no. 6, 2008, pp. 700-9.
Pastorino L, Bonelli L, Ghiorzo P, et al. CDKN2A mutations and MC1R variants in Italian patients with single or multiple primary melanoma. Pigment Cell Melanoma Res. 2008;21(6):700-9.
Pastorino, L., Bonelli, L., Ghiorzo, P., Queirolo, P., Battistuzzi, L., Balleari, E., ... Bianchi Scarrà, G. (2008). CDKN2A mutations and MC1R variants in Italian patients with single or multiple primary melanoma. Pigment Cell & Melanoma Research, 21(6), pp. 700-9. doi:10.1111/j.1755-148X.2008.00512.x.
Pastorino L, et al. CDKN2A Mutations and MC1R Variants in Italian Patients With Single or Multiple Primary Melanoma. Pigment Cell Melanoma Res. 2008;21(6):700-9. PubMed PMID: 18983535.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - CDKN2A mutations and MC1R variants in Italian patients with single or multiple primary melanoma. AU - Pastorino,L, AU - Bonelli,L, AU - Ghiorzo,P, AU - Queirolo,P, AU - Battistuzzi,L, AU - Balleari,E, AU - Nasti,S, AU - Gargiulo,S, AU - Gliori,S, AU - Savoia,P, AU - Abate Osella,S, AU - Bernengo,M G, AU - Bianchi Scarrà,G, Y1 - 2008/10/22/ PY - 2008/11/6/pubmed PY - 2009/1/16/medline PY - 2008/11/6/entrez SP - 700 EP - 9 JF - Pigment cell & melanoma research JO - Pigment Cell Melanoma Res VL - 21 IS - 6 N2 - We evaluated the contribution of germline CDKN2A mutations and MC1R variants to the development of melanoma in a hospital-based study of single (SPM, n = 398) and multiple primary melanoma (MPM, n = 95). The overall frequency of CDKN2A mutations was 15.2%, and four-fold higher in MPM than in SPM cases (OR = 4.27; 95% CI 2.43-7.53). The likelihood of identifying a CDKN2A mutation increased with family history of melanoma and younger age at diagnosis in MPM cases. Compared to SPM patients, the risk of harboring a CDKN2A mutation rose as the number of primary melanomas increased and was not influenced by family history. The G101W and E27X founder mutations were the most common. Several other mutations (W15X, Q50X, R58X, A68L, A127P and H142R) were detected for the first time in Italian patients. One novel mutation, T77A, was identified. Several non-coding variants with unknown functional significance were also found (5'UTR -25C > T, -21C > T, -67G > C, IVS1 +37G > C); the novel 5'UTR -21C > T variant was not detected in controls. The CDKN2A A148T polymorphism was more frequent in MPM patients than in the control population (15.7% versus 6.6%). Compared to the SPM patients, MPM cases had a 2-fold increased probability of being MC1R variant carriers and a higher probability of carrying two or more variants. No specific association was observed between the type of variant and the number of melanomas, suggesting that the number rather than the type of MC1R variant increases the risk of MPM. We observed no interaction between CDKN2A status and the presence of MC1R variants. The high frequency of CDKN2A mutations in our MPM cases, independent of their family history, is of relevance to genetic counseling and testing in our population. SN - 1755-1471 UR - https://www.unboundmedicine.com/medline/citation/18983535/CDKN2A_mutations_and_MC1R_variants_in_Italian_patients_with_single_or_multiple_primary_melanoma_ L2 - https://doi.org/10.1111/j.1755-148X.2008.00512.x DB - PRIME DP - Unbound Medicine ER -