Loss of alleles from the distal short arm of chromosome 1 occurs late in melanoma tumor progression.
The gene for familial malignant melanoma and its precursor lesion, the dysplastic nevus, has been assigned to a region of the distal short arm of chromosome 1, which is frequently involved in karyotypic abnormalities in melanoma cells. We have examined loci on chromosome 1p for loss-of-constitutional heterozygosity in 35 melanomas and 21 melanoma cell lines to analyze the role of these abnormalities in melanocyte transformation. Loss-of-heterozygosity at loci on chromosome 1p was identified in 15/35 (43%) melanomas and 11/21 (52%) melanoma cell lines. Analysis of multiple metastases derived from the same patient and of melanoma and lymphoblastoid samples from a family with hereditary melanoma showed that the loss-of-heterozygosity at loci on distal 1p is a late event in tumor progression, rather than the second mutation that would occur if melanoma were due to a cellular recessive mechanism. Comparisons with neuroblastoma and multiple endocrine neoplasia (MEN2) suggest that the frequent 1p loss-of-heterozygosity in these malignancies is a common late event of neuroectodermal tumor progression.
Dracopoli
N C
NC
Center for Cancer Research, Massachusetts Institute of Technology, Cambridge 02139.
Harnett
P
P
Bale
S J
SJ
Stanger
B Z
BZ
Tucker
M A
MA
Housman
D E
DE
Kefford
R F
RF
D000483:Alleles; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D004273:DNA, Neoplasm / Q000235:genetics; D005260:Female; D006579:Heterozygote; D006801:Humans; D008297:Male; D008545:Melanoma / Q000235:genetics* / Q000473:pathology; D010375:Pedigree
D004273:DNA, Neoplasm