title: 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.
authors: IRCCS Istituto Tumori "Giovanni Paolo II", Molecular Genetics Laboratory, Bari, Italy.
authors: Simona
authors: S
authors: De Summa
authors: IRCCS Istituto Tumori "Giovanni Paolo II", Oncology Unit, Bari, Italy.
authors: Michele
authors: M
authors: Guida
authors: IRCCS Istituto Tumori "Giovanni Paolo II", Molecular Genetics Laboratory, Bari, Italy.
authors: Stefania
authors: S
authors: Tommasi
authors: IRCCS Istituto Tumori "Giovanni Paolo II", Oncology Unit, Bari, Italy.
authors: Sabino
authors: S
authors: Strippoli
authors: University of L'Aquila, Department of Biotechnological and Applied Clinical Sciences, L'Aquila, Italy.
authors: Cristina
authors: C
authors: Pellegrini
authors: University of L'Aquila, Department of Biotechnological and Applied Clinical Sciences, L'Aquila, Italy.
authors: Maria Concetta
authors: MC
authors: Fargnoli
authors: IRCCS Istituto Tumori "Giovanni Paolo II", Molecular Genetics Laboratory, Bari, Italy.
authors: Brunella
authors: B
authors: Pilato
authors: Section of Clinic Pathology, OO.RR., Foggia, Italy.
authors: Iole
authors: I
authors: Natalicchio
authors: University of Bari, Department of Medical Biochemistry, Bari, Italy.
authors: Gabriella
authors: G
authors: Guida
authors: IRCCS Istituto Tumori "Giovanni Paolo II", Molecular Genetics Laboratory, Bari, Italy.
authors: Rosamaria
authors: R
authors: Pinto
mesh_terms: D000417:Albinism / Q000175:diagnosis / Q000235:genetics*; D015415:Biomarkers; D019295:Computational Biology / Q000379:methods; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000737:chemistry / Q000235:genetics; D004252:DNA Mutational Analysis; D045643:DNA Repair Enzymes / Q000737:chemistry / Q000235:genetics; D005190:Family; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D018095:Germ-Line Mutation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D008297:Male; D008545:Melanoma / Q000175:diagnosis / Q000235:genetics*; D008875:Middle Aged; D008958:Models, Molecular; D058977:Molecular Sequence Annotation; D009154:Mutation; D009378:Neoplasms, Multiple Primary / Q000175:diagnosis / Q000235:genetics*; D010375:Pedigree; D010802:Phylogeny; D011487:Protein Conformation; D035781:Siblings; D025521:Tumor Suppressor Proteins / Q000737:chemistry / Q000235:genetics
chemical_list: D015415:Biomarkers; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; D045643:DNA Repair Enzymes
keywords: MGMT; albinism; family study; multiple primary melanoma; susceptibility