Genetic profiling of a rare condition: co-occurrence of albinism and multiple primary melanoma in a caucasian family
Metrics: PDF 1769 views | HTML 1943 views | ?
Simona De Summa1,*, Michele Guida2,*, Stefania Tommasi1, Sabino Strippoli2, Cristina Pellegrini3, Maria Concetta Fargnoli3, Brunella Pilato1, Iole Natalicchio4, Gabriella Guida5, Rosamaria Pinto1
1IRCCS Istituto Tumori “Giovanni Paolo II”, Molecular Genetics Laboratory, Bari, Italy
2IRCCS Istituto Tumori “Giovanni Paolo II”, Oncology Unit, Bari, Italy
3University of L’Aquila, Department of Biotechnological and Applied Clinical Sciences, L’Aquila, Italy
4Section of Clinic Pathology, OO.RR., Foggia, Italy
5University of Bari, Department of Medical Biochemistry, Bari, Italy
*These authors have contributed equally to this work
Stefania Tommasi, email: [email protected]
Keywords: multiple primary melanoma, albinism, MGMT, family study, susceptibility
Received: August 02, 2016 Accepted: October 04, 2016 Published: October 20, 2016
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.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 4.0 License.