Genomic Approaches to Skin Cancer Diagnosis

Cancer Targets in the Ras Pathway

“…Transcription of cyclin D1 is regulated by the MAPK pathway, but cyclin D1 protein is stabilized by the PI3´K pathway; high levels of cyclin D1 protein obviously need inputs from both signaling pathways. Consistent with a role for cyclin D1 in malignant melanoma, this gene is amplified in rare forms of melanoma in which Ras, B-Raf, and PTEN are wild type (Bastian et al 2001).…”

Understanding the progression of melanocytic neoplasia using genomic analysis: from fields to cancer

“…We have previously shown that melanomas in the radial growth phase already show the marked chromosomal aberrations including amplification (Bastian et al, 1998(Bastian et al, , 2000a. If crisis indeed contributes to these aberrations as suspected above, then crisis would have to precede the progression step associated with vertical growth phase.…”

“…Yet another pattern of chromosomal aberrations arose when different types of melanomas were analysed (Bastian et al, 2000a). When compared to the most frequent melanoma type -superficial spreading melanoma -melanomas on acral skin invariably showed gene amplifications.…”

“…In contrast, the few nonacral melanomas that do display amplifications appear to have acquired them later during progression (unpublished data). The amplified regions in acral melanomas frequently contain known oncogenes such as HRAS (Bastian et al, 2000a), cyclin D1 (Sauter et al, in press), CDK4, HTERT, but also involve regions without obvious candidate genes.…”

Ras ubiquitination: Coupling spatial sorting and signal transmission

“…sanger.ac.uk/genetics/CGP/). Activated alleles of N-Ras can lead to metastatic melanoma, whereas activated H-Ras is associated with Spitz nevi that do not progress to malignant disease (Bastian et al, 2000). Germline activating mutations in H-Ras cause Costello syndrome, a developmental disease that is associated with increased incidence of cancer (Aoki et al, 2005), whereas germline mutations in K-Ras can cause Noonan's syndrome (Schubbert et al, 2006).…”