p16INK4a expression and absence of activated B-RAF are independent predictors of chemosensitivity in melanoma tumors.

Metastatic cutaneous melanoma is highly resistant to cytotoxic drugs, and this contributes to poor prognosis. In vivo studies on the chemosensitivity of metastatic melanoma are rare and hampered by poor response rates to systemic chemotherapeutics. Patients who undergo isolated limb infusion (ILI) with cytotoxic drugs show high response rates and are, therefore, a good cohort for studying chemosensitivity in vivo.

Low prevalence of RAS-RAF-activating mutations in Spitz melanocytic nevi compared with other melanocytic lesions.

Melanocytic lesions, including Spitz nevi (SN), common benign nevi (CBN) and cutaneous metastatic melanoma (CMM), were analyzed for activating mutations in NRAS, HRAS and BRAF oncogenes, which induce cellular proliferation via the MAP kinase pathway. One of 22 (4.5%) SN tested showed an HRAS G61L mutation.

Deletion mapping suggests that the 1p22 melanoma susceptibility gene is a tumor suppressor localized to a 9-Mb interval.

Loss of the short arm of chromosome 1 is frequently observed in many tumor types, including melanoma. We recently localized a third melanoma susceptibility locus to chromosome band 1p22. Critical recombinants in linked families localized the gene to a 15-Mb region between D1S430 and D1S2664.

Frequent loss of heterozygosity targeting the inactive X chromosome in melanoma.

After previous preliminary observations of paradoxical deletion events affecting the inactive X chromosome in melanoma, we have surveyed the X chromosome for deletions using 23 polymorphic microsatellite markers in 28 informative (female XX) metastatic melanomas. Ten tumors (36%) showed at least one loss of heterozygosity (LOH) event, and in two cases an entire chromosome showed LOH at all informative loci. Four distinct X chromosome smallest regions of overlap can be resolved.

X inactivation, DNA deletion, and microsatellite instability in common acquired melanocytic nevi.

We have investigated several molecular characteristics of common acquired melanocytic nevi to clarify their relationship to malignant melanoma, which is characterized by clonality and the progressive accumulation of DNA deletions. Twenty-four common acquired nevi were subjected to analysis for loss of heterozygosity at four loci on chromosome 9p and six loci on 10q that are commonly deleted in melanoma, but no deletions were seen. X inactivation analysis was performed in lesions from females, using the methylation-sensitive restriction HpaII site in the CAG microsatellite repeat (HUMARA) in exon 1 of the androgen receptor (AR) gene.