Detection of a rare CDKN2A intronic mutation in a Hungarian melanoma-prone family and its role in splicing regulation

Abstract

We believe that these results confirm the importance of the identification and characterization of CDKN2A intronic mutations with a view to improving our understanding of the pathogenesis, and explain why the frequency of germline coding mutations of the CDKN2A gene is lower than expected in melanoma-prone families linked to chromosome 9p21.

Absence of germlineCDKN2Amutation in Sicilian patients with familial malignant melanoma: Could it be a population-specific genetic signature?

“…[8][9][10] Even rarer deep intronic mutations of CDKN2A have also been described, although these account for very few cases worldwide. [11][12][13][14] INK4A is a cyclin-dependent kinase inhibitor that activates the pRB protein via negative regulation of Cdk4/6, promoting the progression through the G1/S transition, whereas p14ARF interacts with the MDM2 protein, whose principal function is to promote the ubiquitin-mediated degradation of the tumorsuppressor protein p53. 15,16 Thus, the loss of function of p16 INK4a promotes CDK4 and CDK6 activation, causing hyperphosphorylation and inactivation of retinoblastoma protein (pRB), and activation of E2F1 ( Fig.…”