|
Research
Research conducted in our laboratory focuses upon the identification and functional analysis of genes that govern melanoma development and progression. The stages defining melanoma progression are: atypical nevi - melanoma in situ - primary melanoma in the radial growth phase (RGP melanoma) - primary melanoma in the vertical growth phase (VGP melanoma) - melanoma in the metastatic growth phase (MGP melanoma). To unravel the molecular signature of the nevocytic and melanocytic lesions defining these stages, we have performed Serial Analysis of Gene Expression (SAGE), and whole-human genome microarray and proteomic profiling. The results of the whole-human genome microarray analysis of tissue samples ranging from normal skin to melanoma-infiltrated lymph nodes revealed two molecular profiles - one that characterizes normal skin, benign and atypical nevi, and melanoma in situ, and the other, VGP and MGP melanomas, including melanoma-infiltrated lymph nodes. Furthermore, the data from these whole-human genome microarray studies documented that the most prominent events associated with this switch from one molecular profile to the other, are aberrant changes in the mitotic cell cycle. Using molecular studies, including RNA interference, antisense technology, gene targeting with small molecule inhibitors as well as optical imaging, we are determining both in vitro and in preclinical studies involving human melanoma xenografts, the role of genes identified by these high-throughput studies in advanced-stage melanoma.
Distribution by Biologic Function of Transcripts Identified in a
VGP (DB2) and an MGP (DB4) Melanoma SAGE Library
Whole-Genome Microarray Analysis Reveals Two Expression Patterns
Gene Ontology (GO) Groups Characterizing Progression to Advanced-Stage Melanoma
 |
 |
 |
 |
| Gene Ontology Group |
Total in SOM |
Number in GO |
Z Score |
| mitotic cell cycle |
14 |
382 |
4.680 |
| cell proliferation |
29 |
1104 |
4.134 |
| cell cycle |
21 |
757 |
3.959 |
| DNA replication and chromosome cycle |
8 |
239 |
3.501 |
| nuclear division |
7 |
152 |
3.269 |
| M phase |
7 |
162 |
3.269 |
| M phase of mitotic cell cycle |
7 |
125 |
3.269 |
| mitosis |
7 |
121 |
3.269 |
|
 |
 |
 |
 |
|
