CDKN2A/CDK4 status in Brazilian patients meeting clinical criteria for hereditary melanoma: a cross‐sectional descriptive trial

• Published in: International journal of dermatology 2023-08, Vol.62 (8), p.1060-1066
• Main Authors: Arnaut, Joyce R. M. B., Guimarães, Isabella dos S., Santos, Anna Cláudia E., Rodrigues, Elizângela M., Machado, Jorge R. da S., Melo, Andreia C.
• Format: Article
• Language: English
• Subjects: 3' Untranslated regions; 5' Untranslated Regions; Adult; Brazil - epidemiology; Cancer; Criteria; Cross-Sectional Studies; Cyclin-dependent kinase 4; Cyclin-Dependent Kinase 4 - genetics; Cyclin-Dependent Kinase Inhibitor p16 - genetics; Exons; Genetic Predisposition to Disease; Genetics; Germ-Line Mutation; Humans; Melanoma; Melanoma - epidemiology; Melanoma - genetics; Melanoma - pathology; Melanoma, Cutaneous Malignant; Mutation; Nevus; Pancreatic cancer; Patients; Skin cancer; Skin Neoplasms - epidemiology; Skin Neoplasms - genetics; Skin Neoplasms - pathology; Sunburn; Tumors
• ISSN: 0011-9059; 1365-4632
• DOI: 10.1111/ijd.16742

Background Melanoma is the most lethal skin cancer, and its incidence has increased worldwide. About 10% of cases are classified as hereditary melanoma (HM). CDKN2A and CDK4 are the major high‐risk genes. Families are also more prone to develop pancreatic cancer, and different forms of oncological surveillance are recommended. Objectives Describe the prevalence of CDKN2A/CDK4 germline mutations in melanoma‐prone patients and their phenotypic and histopathological features. Methods A total of 69 patients meeting the clinical criteria for HM were included in this cross‐sectional descriptive study. Amplification by PCR and genomic sequencing were used. The variants were classified according to American College of Medical Genetics (ACMG) criteria. 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%). Two hundred 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 seven patients (c.305C>A, c.26T>A, c.361G>A e c.442G>A), two variants in the 5′UTR region in five patients (c.‐25C>T and c.‐33G>C), and two variants in the 3′UTR region in 21 patients (c.*29C>G and c.*69C>T). One likely pathogenic variant (c.305C>A) was identified in one patient (1.4%). No variant was found in CDK4. Conclusion The prevalence of CDKN2A mutations was 1.4% in Brazilian patients meeting clinical criteria for HM.