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Allelotyping, Microsatellite Instability, and BRAF Mutation Analyses in Common and Atypical Melanocytic Nevi and Primary Cutaneous Melanomas

Uribe, Pablo MD, PhD*; Wistuba, Ignacio I MD*†; Gonzalez, Sergio MD*

American Journal of Dermatopathology: June 2009 - Volume 31 - Issue 4 - pp 354-363
doi: 10.1097/DAD.0b013e318185d205
Original Study

Loss of heterozygosity (LOH) in several chromosomal regions is found in melanoma, and it has been partially studied in nevi. BRAF mutations are found in melanoma and nevi and in colorectal cancer are linked to mismatch repair deficiency. We studied early genetic events involved in melanomagenesis through analysis of allelic loss, microsatellite instability (MSI), and BRAF mutations.

DNA extracted from microdissected cells of 22 common nevi, 23 atypical nevi, and 25 primary cutaneous melanomas were examined for LOH and MSI by polymerase chain reaction-based analysis of 24 microsatellite markers and BRAF mutation. Allelic loss index was higher in atypical nevi (0.20) and melanomas (0.27) than common nevi (0.07). LOH was frequent at 9p21, 17q21, 6q23, and 5q35 in melanoma. LOH at any of this loci occurred in 27% of common nevi, 57% of atypical nevi, and 68% of melanomas. BRAF mutations were not related to MSI presence and MSI index was not related with BRAF mutational status. Similar genetic alterations in atypical nevi and melanomas support the concept of atypical nevus as melanoma precursor. Novel deletion loci at 5q35 and 17q21 (BRCA1) in atypical nevi and melanomas were identified. Mismatch repair deficiency is not a crucial event for BRAF mutation in melanocytic tumors.

*From the Departamento de Anatomía Patológica, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.

†Present address: Departments of Pathology and Thoracic/Head and Neck Medical Oncology, MD Anderson Cancer Center, Houston, TX.

Supported in part by grants FONDECYT 1020696 (Fondo Nacional de Desarrollo Científico y Tecnológico, Chile) (S.G.) and PG-04/02 (Facultad de Medicina, Pontificia Universidad Católica de Chile) (P.U.).

The authors state no conflict of interest.

Reprints: Sergio Gonzalez, MD, Professor of Pathology, Department of Anatomic Pathology, Pontificia Universidad Católica de Chile, 85 Lira Street, Fourth Floor, 2550681 Santiago, Chile (e-mail: sgonzale@med.puc.cl).

© 2009 Lippincott Williams & Wilkins, Inc.