Date of Award

10-30-2009

Document Type

Thesis

Degree Name

Medical Doctor (MD)

First Advisor

Joanne Weidhaas MD

Abstract

While it has been shown that alterations in miRNA expression profiles can serve as phenotypic signatures of a particular cancer, there are little available data concerning melanoma. This study was designed to investigate the relative expression of normal adult melanocytes, newborn amelanotic foreskin melanocytes and several subtypes of melanoma: acral, nodular and mucosal. Our hypothesis is that up- and/or down-regulation of individual microRNAs will elucidate potential genetic mediators by which melanoma develops based on existing knowledge of their downstream molecular targets as well as provide a scheme by which subtypes of melanoma may be diagnosed and uniquely treated. Microarray-based miRNA profiling of adult and newborn melanocytes and melanoma cell lines, of primary or metastatic origin, was performed. Newborn melanocytes appeared to have higher levels of expression of many miRNAs, consistent with the role miRNAs play in development and differentiation of tissues. Melanoma exhibited upregulation of the oncogenes mir-222, mir-21 and mir-20a and downregulation of the known tumor suppressor, miR-16 relative to benign controls. Furthermore, the acral lentiginous melanoma samples displayed underexpression of several miRNAs when compared with normal melanocytes and other subtypes, providing potential for investigating the contribution of these miRNAs to the unique clinicpathological characteristics of this subtype.

Comments

This thesis is restricted to Yale network users only. This thesis is permanently embargoed from public release.

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