Melanoma-astrocytoma syndrome ... (melanoma-Astrocytoma syndrome, melanoma and neural system tumor syndrome) - CDKN2A
Melanoma-astrocytoma syndrome is characterized by a dual predisposition to develop melanomas and tumors, astrocytoma often nervous system. Its actual impact on the population is unknown, although it is more common in individuals of Jewish origin.
The gene associated with the development of this syndrome is CDKN2A (Cyclin-dependent kinase inhibitor 2A), located on the short arm of chromosome 9 (9p21). This is the same gene as that to which mutations, somatic or congenital, associated with the development of malignant cutaneous melanomas are associated - see cutaneous malignant melanoma - Genes CDKN2A and CDK4-. This gene has the ability to generate two proteins via alternative splicing (cutting and sealing) the first exon: p16, encoded by 1? exons 2 and 3, is involved in cell cycle control and apoptosis, and p14 ARF, encoded by exons 1?, 2 and 3, whose role is in cell cycle regulation through a p53 - dependent pathway. P16 protein binds competitively inhibits the cyclin dependent kinases (CDK4 and CDK6). For this reason it is also sometimes called INK4a (kinase inhibitor 4). Thus achieved prevent complex formation formed by the union of CDK4 and cyclin D1, necessary for the transition from the G1 phase of the cell cycle phase S.
Mutations associated with melanoma-astrocytoma syndrome are largely germ deletions relatively large chromosome region 9p21, where CDKN2A included. They have also been reported that include only exon 1?, corresponding to the p14 isoform, which suggests that the fundamental anomaly for the development of melanoma-astrocytoma syndrome is the loss of p14 isoform.
Melanoma-astrocytoma syndrome is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient for the process to be expressed. However, in some cases, the pattern of inheritance is unknown.
Tests performed in IVAMI: in IVAMI perform detection of any genetic abnormality associated with melanoma-astrocytoma syndrome. First we recommend starting the study looking for deletions in chromosome 9p21 region where the CDKN2A gene is using the technique of quantitative real - time PCR (qPCR Real Time). If negative result is the possibility of carrying out the sequence analysis CDKN2A complete by PCR amplification followed by direct sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).