A germline deletion of 9p21.3 presenting as familial melanoma, astrocytoma and breast cancer: clinical and genetic counselling challenges

Baker and collaborators describe a family with melanomas, nerve sheath tumours, gliomas and haematological malignancies caused by a large, 25-gene deletion resulting from an unbalanced translocation in 9p21.3.1 The 9p21.3 region contains at least three tumour suppressor genes: CDKN2A, CDKN2B and MTAP. Somatic deletions involving this region have been identified in tumours such as breast, prostate, melanoma, leukaemia, among many. Germline mutations and deletions involving the genes in this region are causative of inherited cancer predisposition. We report the case of a family with a germline 9p21.3 deletion encompassing nine genes. The family presented with melanomas, astrocytomas, neurofibromas and breast cancer.

The CDKN2A gene encodes two proteins: p16 and p14, by means of alternative splicing. Protein p16 inhibits cyclin-dependent kinase 4 (CDK4) which controls the progression through the G1 phase of the cell cycle by phosphorylating Rb.2 In turn, p14 is a stabiliser of p53—a key protein...

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