Article Text

Download PDFPDF
A germline deletion of 9p21.3 presenting as familial melanoma, astrocytoma and breast cancer: clinical and genetic counselling challenges
  1. Jaime Vengoechea,
  2. Christine Tallo
  1. Human Genetics, Emory University, Atlanta, Georgia, USA
  1. Correspondence to Dr. Jaime Vengoechea, Human Genetics, Emory University, 1365 Clifton Rd NE, Building A, Suite 1500, Atlanta, Georgia 30322, USA; jvengoe{at}

Statistics from

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

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 in inducing cell apoptosis.3 CDKN2B encodes p15, which similarly inhibits CDK4 and CDK6.4 MTAP encodes methylthioadenosine phosphorylase—an enzyme that appears to also exhibit features of a tumour suppressor gene.

Mutations affecting the p16 transcript of CDKN2A can cause familial atypical multiple mole melanoma syndrome5 also known as pancreatic cancer–melanoma syndrome.6 Melanoma–astrocytoma syndrome (MAS) presents with melanomas, astrocytoma, neurofibromas, …

View Full Text


  • Competing interests None declared.

  • Patient consent Obtained.

  • Ethics approval Emory IRB.

  • Provenance and peer review Not commissioned; externally peer reviewed.