CDKN2A/CDK4 STATUS IN BRAZILIAN PATIENTS MEETING CLINICAL CRITERIA FOR HEREDITARY MELANOMA

Keywords:

melanoma - hereditary melanoma - familial melanoma - CDKN2A - CDK4 - melanoma genetics - genetic counseling - genetic testing.

Introduction: Melanoma is considered the most lethal skin cancer and its incidence has increased during the past decades. About 10% of cases are classifi+B2:J3ed as hereditary melanoma (HM). Several genes have been identified as involved to melanoma susceptibility. CDKN2A and CDK4 were the first high-risk genes discovered. Beyond melanoma, families are also more prone to develop other malignancies, such as pancreatic cancer. The identification of risk families and involved genes is of great importance, since different forms of oncological surveillance are recommended. Objectives: Identify the prevalence of germline mutations in CDKN2A and CDK4 in INCA patients meeting clinical criteria for HM. Describe the phenotypic and histopathological characteristics. Materials and methods: The study design was cross-sectional descriptive. A total of 69 patients meeting clinical criteria for HM were included. For mutational analysis of genes, amplification by polymerase chain reaction (PCR) followed by genomic sequencing was used. The variants found were classified according to their pathogenicity using the criteria of the American College of Medical Genetics. Results:The mean age at first diagnosis of melanoma was 44.8 years (SD±17.83). Most patients had phototype II (44.9%), more than 50 melanocytic nevi (76.8%), atypical nevus syndrome (72.5%), history of sunburn (76.8%) and multiple primary melanomas without a family history of this tumor (74.3%). 200 melanomas were observed. Most tumors had a Breslow index ≤ 1.0 mm (84.5%), location in the trunk (60.5%) and superficial spreading histological subtype (22.5%). Four variants were found in CDKN2A exons in 7 patients (c.305C>A, c.26T>A, c.361G>A e c.442G>A), 2 variants in the 5'UTR region in 5 patients (c.-25C>T and c.-- 33G>C) and 2 variants in the 3’UTR region in 21 patients (c.*29C>G and c.*69C>T). Only one likely pathogenic variant (c.305C>A) was identified in one patient (1.4%). No variant was found in CDK4. Discussion: This is the first study about HM carried out in Rio de Janeiro. In Brazil, it is the largest single-center cohort of patients meeting clinical criteria for HM submitted to the search for variants in the CDKN2A and CDK4 genes. The low prevalence of mutations can be explained by limitations of this study. The findings are consistent with published Brazilian data. Conclusion: The prevalence of mutations in the CDKN2A gene was 1.4% in the INCA patient population meeting clinical criteria for HM.

 

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No conflict of interest has been declared by the author(s).

Publication History

Article published online:
03 November 2022