Multiple melanomas after treatment for Hodgkin lymphoma in a non-Dutch p16-Leiden mutation carrier with 2 MC1R high-risk variants

• Verfasst von: Figl, Adina [VerfasserIn]
• Verfasst von: Ugurel, Selma [VerfasserIn]
• Verfasst von: Gast, Andreas [VerfasserIn]
• Verfasst von: Hemminki, Kari [VerfasserIn]
• Verfasst von: Kumar, Rajiv [VerfasserIn]
• Verfasst von: Schadendorf, Dirk [VerfasserIn]
• Titel: Multiple melanomas after treatment for Hodgkin lymphoma in a non-Dutch p16-Leiden mutation carrier with 2 MC1R high-risk variants
• Verf.angabe: Adina Figl, Ranjit K. Thirumaran, Selma Ugurel, Andreas Gast, Kari Hemminki, Rajiv Kumar, Dirk Schadendorf
• Jahr: 2007
• Umfang: 5 S.
• Fussnoten: Gesehen am 05.02.2021
• Titel Quelle: Enthalten in: Archives of dermatology
• Ort Quelle: Chicago, Ill. : AMA, 1960
• Jahr Quelle: 2007
• Band/Heft Quelle: 143(2007), 4, Seite 495-499
• ISSN Quelle: 1538-3652
• DOI: doi:10.1001/archderm.143.4.495
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Adult
• Sach-SW: Cyclin-Dependent Kinase Inhibitor p16
• Sach-SW: Female
• Sach-SW: Genes, p16
• Sach-SW: Genetic Predisposition to Disease
• Sach-SW: Germ-Line Mutation
• Sach-SW: Hodgkin Disease
• Sach-SW: Humans
• Sach-SW: Loss of Heterozygosity
• Sach-SW: Melanoma
• Sach-SW: Neoplasms, Multiple Primary
• Sach-SW: Pedigree
• Sach-SW: Penetrance
• Sach-SW: Receptor, Melanocortin, Type 1
• Sach-SW: Skin Neoplasms
• K10plus-PPN: 1747463396

Abstract

BACKGROUND: A 19-base pair germline deletion in exon 2 of the CDKN2A (cyclin-dependent kinase inhibitor 2A) gene (Leiden mutation) has been detected in Dutch families with familial melanomas. The penetrance of CDKN2A mutations varies widely and is influenced by environmental and unrelated genetic factors such as variants in the MC1R gene. - OBSERVATIONS: We describe a 25-year-old German woman who developed 8 invasive melanomas and 6 in situ melanomas after radiation therapy and polychemotherapy for Hodgkin lymphoma. Genetic testing revealed a constitutional CDKN2A Leiden mutation in the proband and her sister, mother, and mother's sister. The proband also carried high-risk MC1R variant alleles R151C and R160W, which she had inherited from her father and her mother, respectively. The less affected mutation carrier sister did not have high-risk MC1R variant alleles. Analysis of DNA from paraffin-embedded tissues showed loss of heterozygosity at CDKN2A loci in all 3 melanomas studied but not in Hodgkin lymphoma. The pedigree revealed several types of cancers on both sides of the family, but no Dutch ancestors were found. No mutations in the CDK4, B-raf, and N-ras genes were detected either in the germline or in tumors from the patient. - CONCLUSION: This study shows the variability of the penetrance of the CDKN2A Leiden mutation within the same family, which could be due to genetic or exogenous factors.