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- Title
Chromosome 17 Allelic Loss and <em>NF1</em>-GRD Mutations Do Not Play a Significant Role as Molecular Mechanisms Leading to Melanoma Tumorigenesis.
- Authors
Gómez, Lourdes; Rubio, Mari-Paz; Martin, M. Teresa; Vázquez, J. Jaime; Idoate, Miguel; Pastorfide, Georgina; Pestaña, Angel; Seizinger, Bernd R.; Barnhill, Raymond L.; Castresana, Javier S.
- Abstract
Allelic loss in human cutaneous melanoma has been detected on chromosomes 1p, 6q, 9p, 10q, and 11q. Chromosome 17 contains important tumor suppressor genes such as p53, <em>NM23</em>, and neurofibromatosis type 1 (<em>NF1</em>), which have been implicated in melanoma tumorigenesis. The role of p53 has already been studied by a number of laboratories, showing contrasting results. In the present study, two restriction fragment length polymorphism (RFLP) probes for the <em>NM23</em> and <em>NF1</em> genes, together with five other RFLP and four variable number of tandem repeat chromosome 17 probes, were investigated at the loss of heterozygosity (LOH) level in a Southern blot-based assay. The <em>NF1</em> gene was also tested for LOH by a polymerase chain reaction (PCR)-based approach in two different experiments, using a dinucleotide repeat polymorphic probe at locus D17S250 (17q11.2- q12), and an Alu probe intragenic to the <em>NF1</em> gene (17q11.2). A PCR single-strand conformation polymorphism assay was included in the study for mutation detection at the <em>NF1</em>-GTPase-activating protein-related domain (GRD). A total of 68 melanocytic tumors were analyzed. LOH was detected in 9 of 87 informative cases (10%). LEW301 (17p11.2-pcen) presented the highest LOH frequency (22%). <em>NM23</em> showed LOH in 17% of the informative cases, while <em>NF1</em> did not show either LOH in the Southern blot- and PCR-based experiments or mutations at the <em>NF1</em>- GRD. These results are in concordance with those of previous smaller studies, but when compared with higher LOH frequencies obtained from other chromosomes, these findings indicate that the LOH values found in our study can most likely be attributed to background effect. Thus, chromosome 17 LOH is likely to play an unimportant role as a genetic event in melanoma tumorigenesis. Nevertheless, <em>NF1</em> merits further study, since homozygous deletions have been detected at this locus in melanoma cell lines.
- Subjects
POLYMERASE chain reaction; SKIN cancer; MELANOMA; CHROMOSOMES; NEUROFIBROMATOSIS; GENES
- Publication
Journal of Investigative Dermatology, 1996, Vol 106, Issue 3, p432
- ISSN
0022-202X
- Publication type
Article
- DOI
10.1111/1523-1747.ep12343578