TY - JOUR
T1 - Loss of heterozygosity analysis of cutaneous melanoma and benign melanocytic nevi
T2 - Laser capture microdissection demonstrates clonal genetic changes in acquired nevocellular nevi
AU - Maitra, Anirban
AU - Gazdar, Adi F.
AU - Moore, Todd O.
AU - Moore, Angela Yen
N1 - Funding Information:
This work has been supported by a generous grant from the Dermatology Foundation.
PY - 2002
Y1 - 2002
N2 - The molecular pathology of the common nevocellular nevus (NCN) and its relationship to the genetic model of malignant melanoma (MM) progression has not been fully characterized. We used laser capture microdissection of archival formalin-fixed material to study 34 melanocytic lesions (19 MM and 15 NCN). Twelve of the 15 NCN were acquired, 3 of which were congenital; none had dysplastic features. Ten polymorphic markers on five chromosomal regions (1p36, 6q22-23.3, 8p22-24, 10q23, and 11q23) were selected for loss of heterozygosity (LOH) analysis, based on previous studies demonstrating involvement in MM pathogenesis and progression. Loss of heterozygosity at any allelic locus was observed in 18 of 19 (95%) MM and in 9 of 15 (60%) NCN. Of the three congenital nevi analyzed, none showed LOH at any informative locus. The frequency of allelic loss was highest in the MM at 6q22-23.3 (64%), followed by 10q23 (62%), 8p22-24 (43%), 11q23 (43%), and 1p36 (13%). In the 15 NCN, the most frequent allelic losses were detected at 6q22-23.3 (29%), 1p36 (27%), and 10q23 (25%), with lower frequencies of LOH at 11q23 (10%) and 8p22-24 (7%). LOH at a single polymorphic marker, D6S1038, was detected in 70% of the MM and in 36% of the NCN, suggesting the presence of putative tumor-suppressor genes (TSGs) critical in melanocytic neoplasia at 6q22-23.3. The presence of clonal genetic alterations in acquired NCN justifies their classification as a benign neoplasm. The pattern of LOH in NCN is not random; rather, the relative frequencies of LOH at the chromosomal regions examined are consistent with a multistep model of MM progression that begins with NCN. Molecular analysis of NCN reiterates established epidemiologic and morphologic notions that NCN are precursor lesions for MM.
AB - The molecular pathology of the common nevocellular nevus (NCN) and its relationship to the genetic model of malignant melanoma (MM) progression has not been fully characterized. We used laser capture microdissection of archival formalin-fixed material to study 34 melanocytic lesions (19 MM and 15 NCN). Twelve of the 15 NCN were acquired, 3 of which were congenital; none had dysplastic features. Ten polymorphic markers on five chromosomal regions (1p36, 6q22-23.3, 8p22-24, 10q23, and 11q23) were selected for loss of heterozygosity (LOH) analysis, based on previous studies demonstrating involvement in MM pathogenesis and progression. Loss of heterozygosity at any allelic locus was observed in 18 of 19 (95%) MM and in 9 of 15 (60%) NCN. Of the three congenital nevi analyzed, none showed LOH at any informative locus. The frequency of allelic loss was highest in the MM at 6q22-23.3 (64%), followed by 10q23 (62%), 8p22-24 (43%), 11q23 (43%), and 1p36 (13%). In the 15 NCN, the most frequent allelic losses were detected at 6q22-23.3 (29%), 1p36 (27%), and 10q23 (25%), with lower frequencies of LOH at 11q23 (10%) and 8p22-24 (7%). LOH at a single polymorphic marker, D6S1038, was detected in 70% of the MM and in 36% of the NCN, suggesting the presence of putative tumor-suppressor genes (TSGs) critical in melanocytic neoplasia at 6q22-23.3. The presence of clonal genetic alterations in acquired NCN justifies their classification as a benign neoplasm. The pattern of LOH in NCN is not random; rather, the relative frequencies of LOH at the chromosomal regions examined are consistent with a multistep model of MM progression that begins with NCN. Molecular analysis of NCN reiterates established epidemiologic and morphologic notions that NCN are precursor lesions for MM.
KW - Chromosome 6q
KW - Loss of heterozygosity
KW - Malignant melanoma
KW - Microdissection
KW - Nevocellular nevi
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U2 - 10.1053/hupa.2002.31297
DO - 10.1053/hupa.2002.31297
M3 - Article
C2 - 11957144
AN - SCOPUS:0036219402
SN - 0046-8177
VL - 33
SP - 191
EP - 197
JO - Human Pathology
JF - Human Pathology
IS - 2
ER -