Genomic Approaches to Skin Cancer Diagnosis

Bastian, Boris C.; LeBoit, Philip E.; Pinkel, Dan

doi:10.1001/archderm.137.11.1507

Cited by 16 publications

(6 citation statements)

References 32 publications

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“…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).…”

Section: Cancer Genetics and Ras Effectorsmentioning

confidence: 61%

Cancer Targets in the Ras Pathway

Rodríguez‐Viciana¹,

Tetsu²,

Oda³

et al. 2005

Cold Spring Harbor Symposia on Quantitative Biology

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Section: Cancer Genetics and Ras Effectorsmentioning

confidence: 61%

Cancer Targets in the Ras Pathway

Rodríguez‐Viciana¹,

Tetsu²,

Oda³

et al. 2005

Cold Spring Harbor Symposia on Quantitative Biology

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“…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.…”

Section: Telomeric Crisis and Regression Of Melanomamentioning

confidence: 75%

“…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.…”

Section: Patterns Of Chromosomal Aberrations In Melanocytic Neoplasmsmentioning

confidence: 99%

“…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the few nonacral melanomas that do display amplifications appear to have acquired them later during progression (unpublished data).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.…”

Section: Patterns Of Chromosomal Aberrations In Melanocytic Neoplasmsmentioning

confidence: 99%

“…The fact that all AM in our study had at least one, mostly several, amplifications suggested that amplifications arise early during progression. We performed extensive FISH studies on the tumors that we had profiled by CGH to map topographically the amplifications on tissue sections (Bastian et al, 2000a). We found that the amplifications were present at mostly similar levels in the invasive areas, areas of radial growth, and the in situ portion of the cases.…”

Section: Telomeric Crisis and Regression Of Melanomamentioning

confidence: 99%

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

Bastian

2003

Oncogene

116

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Analysis of DNA copy number changes using comparative genomic hybridization in melanocytic neoplasms has revealed distinct patterns of chromosomal aberrations between benign melanocytic nevi and melanoma. Whereas the vast majority of melanoma expresses chromosomal aberrations, blue nevi, congenital nevi, and most Spitz nevi typically show no aberrations. A subset of Spitz nevi shows an isolated gain of chromosome 11p, an aberration pattern not observed in melanoma. These Spitz nevi frequently harbor mutations in the HRAS gene located on this chromosomal arm. Comparisons among melanoma types showed that melanomas of the palms, soles, and subungual sites can be distinguished by the presence of multiple gene amplifications that arise very early in their progression. About 50% of these amplifications are found at the cyclin D1 locus. By contrast, amplifications are significantly less frequent in other cutaneous melanoma types and if present arise late in progression. The frequent amplifications in melanomas on acral sites allowed the detection of single basal melanocytes with gene amplifications in the histologically normal appearing skin immediately adjacent to a melanoma. These ''field cells'' represent subtle melanoma in situ and are likely to represent minimal residual disease that can lead to local recurrences if not excised with safety margins. The high frequency of chromosomal aberrations in melanomas and their relative absence in nevi could indicate that melanocytes of melanomas went through telomeric crisis, whereas melanocytes in nevi did not. Such a scenario would suggest that replicative senescence is a tumor-suppressive mechanism in melanocytic neoplasia. It might also explain part of the phenomenon of regression commonly seen in melanoma.Genomic analysis is a powerful tool to obtain insight in the progression of melanocytic neoplasms with potential clinical applications for classification and detection of minimal residual melanoma. Oncogene (2003) 22, 3081-3086. doi:10.1038/sj.onc.1206463Keywords: melanoma; Spitz nevus; genetics; regression; minimal residual disease Patterns of chromosomal aberrations in melanocytic neoplasmsWe have used comparative genomic hybridization (CGH) to perform genome-wide searches for patterns of aberrations that may be of help in the classification of melanocytic neoplasms. Using chromosome and arraybased CGH we have analysed several hundreds of benign and malignant melanocytic skin tumors. CGH can detect and map changes in DNA copy number in DNA samples including DNA extracted from archival specimens. Whereas the vast majority of melanomas showed chromosomal aberrations, the benign nevi mostly did not show aberrations. Whereas congenital nevi (Bastian et al., in press) and blue nevi (manuscript in preparation) did not show aberrations at all, a subset of Spitz nevi (about 20%) showed an isolated gain of chromosome 11p (Bastian et al., 1999). The remainder of the Spitz nevi also did not show aberrations. Recent studies showed that this gain was because of the presence of mu...

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Hypothesis: A Role for Telomere Crisis in Spontaneous Regression of Melanoma

Bastian¹

2003

Arch Dermatol

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Genomic Approaches to Skin Cancer Diagnosis

Cited by 16 publications

References 32 publications

Cancer Targets in the Ras Pathway

Cancer Targets in the Ras Pathway

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

Hypothesis: A Role for Telomere Crisis in Spontaneous Regression of Melanoma

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