TY - JOUR
T1 - Comparative analysis of loss of heterozygosity and microsatellite instability in adult and pediatric melanoma
AU - Uribe, Pablo
AU - Wistuba, Ignacio I.
AU - Solar, Antonieta
AU - Balestrini, Claudia
AU - Perez-Cotapos, Maria Luisa
AU - Gonzalez, Sergio
N1 - Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/8
Y1 - 2005/8
N2 - Although 0.3% of melanomas occur in children, the incidence has risen in past decades. In adult melanoma, some chromosomal regions in 1p, 6q, 9p, 10q, and 11q are frequently deleted. Microsatellite instability (MSI), which reflects impaired DNA repair, has been found at low levels in adult melanoma and melanocytic nevi. To investigate the molecular changes in pediatric melanoma, a screening for loss of heterozygosity and microsatellite instability was performed and compared with changes found in adult melanoma. Formalin-fixed, paraffin-embedded tissues from 10 adult melanomas, 9 melanocytic nevi, and 8 pediatric melanomas were microdissected and the DNA was extracted. Loss of heterozygosity and microsatellite instability were evaluated using 13 microsatellite repeat polymorphisms located in 1p36, 1q32, 2p12, 2p22-25, 2q33-37, 9p21, 10q23.3, 11q23, 13q14, 17p13, and 17q21. The overall frequency of loss of heterozygosity was 0.09 for nevi, 0.30 for adult melanoma, and 0.43 for pediatric melanoma (nevi vs. adult melanoma, P = 0.0082; nevi vs. pediatric melanoma, P = 0.0092). Pediatric melanoma has more loss of heterozygosity (44%) in 11q23 than adult melanoma (7%, P = 0.046). The microsatellite instability overall frequency was greater in pediatric melanoma (0.24) than nevi (0.05, P = 0.0031) and adult melanoma (0.09, P = 0.0195). Our findings suggest that pediatric melanoma has a different abnormal pattern than adult melanoma. Pediatric melanoma has more microsatellite instability than adult melanoma. 11q23 could contain genes related to the early age onset of melanoma. The high frequency of microsatellite instability is coincidental with the finding of higher levels of microsatellite instability in pediatric brain tumors and could play a role in the pathogenesis of pediatric melanoma.
AB - Although 0.3% of melanomas occur in children, the incidence has risen in past decades. In adult melanoma, some chromosomal regions in 1p, 6q, 9p, 10q, and 11q are frequently deleted. Microsatellite instability (MSI), which reflects impaired DNA repair, has been found at low levels in adult melanoma and melanocytic nevi. To investigate the molecular changes in pediatric melanoma, a screening for loss of heterozygosity and microsatellite instability was performed and compared with changes found in adult melanoma. Formalin-fixed, paraffin-embedded tissues from 10 adult melanomas, 9 melanocytic nevi, and 8 pediatric melanomas were microdissected and the DNA was extracted. Loss of heterozygosity and microsatellite instability were evaluated using 13 microsatellite repeat polymorphisms located in 1p36, 1q32, 2p12, 2p22-25, 2q33-37, 9p21, 10q23.3, 11q23, 13q14, 17p13, and 17q21. The overall frequency of loss of heterozygosity was 0.09 for nevi, 0.30 for adult melanoma, and 0.43 for pediatric melanoma (nevi vs. adult melanoma, P = 0.0082; nevi vs. pediatric melanoma, P = 0.0092). Pediatric melanoma has more loss of heterozygosity (44%) in 11q23 than adult melanoma (7%, P = 0.046). The microsatellite instability overall frequency was greater in pediatric melanoma (0.24) than nevi (0.05, P = 0.0031) and adult melanoma (0.09, P = 0.0195). Our findings suggest that pediatric melanoma has a different abnormal pattern than adult melanoma. Pediatric melanoma has more microsatellite instability than adult melanoma. 11q23 could contain genes related to the early age onset of melanoma. The high frequency of microsatellite instability is coincidental with the finding of higher levels of microsatellite instability in pediatric brain tumors and could play a role in the pathogenesis of pediatric melanoma.
KW - Childhood melanoma
KW - Cutaneous melanoma
KW - Loss of heterozygosity
KW - Microsatellite instability
KW - Pediatric melanoma
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U2 - 10.1097/01.dad.0000171599.40562.7c
DO - 10.1097/01.dad.0000171599.40562.7c
M3 - Article
C2 - 16121045
AN - SCOPUS:24144441243
SN - 0193-1091
VL - 27
SP - 279
EP - 285
JO - American Journal of Dermatopathology
JF - American Journal of Dermatopathology
IS - 4
ER -