P17.79A MELANOMA-ASTROCYTOMA SYNDROME ASSOCIATED TO A CONSTITUTIVE MICRODUPLICATION ON 5P15.33, CONTAINING THE TERT GENE

Melanoma-astrocytoma syndrome (OMIM #155755) is characterized by association of cutaneous malignant melanoma and tumors of central nervous system, generally astrocytomas. The deletion of tumor-suppressor genes on chromosomal region 9p21 (p15/CDKN2B, p16/CDKN2A and p14/ARF) is often reported in families with hereditary predisposition to melanoma and nervous system tumors. We describe a family including a patient with history of melanoma and low grade glioma not associated with mutation on 9 chromosome. The proband is a 40 year old woman who underwent surgery for a cervical cutaneous melanoma. After 4 months, during oncological follow-up, an asymptomatic, left frontal cerebral lesion was detected and subsequently excised. Histopathology indicated a WHO grade II oligoastrocytoma, with 1p/19q deletion and mutation of IDH1 (PCR). In her family there is another case of malignant melanoma (grandfather) and two cases of multiple cutaneus basaliomas (mother and her 33 year-old sister). Array-CGH on lymphocyte DNA was performed, using Cytochip ISCA 4 x 180K platform (Bluegnome). This study revealed the presence of a 1.2 Mb microduplication on 5p15.33, including telomerase reverse transcriptase (TERT) gene. The same duplication was found in the mother DNA. TERT is up-regulated in a variety of human cancers, including melanomas and gliomas. Among gliomas, TERT point mutations, associated to increased expression of the gene, were found in 80% of primary glioblastomas and 78% of oligodendrogliomas. To our knowledge this is the first report of melanoma-astrocytoma syndrome associated to amplification on 5p15.33. Interestingly, genome wide association studies have found rs2736100, also located on 5p15.33, as a susceptibility locus for gliomas.