The Impact of Genomics in Understanding Human Melanoma Progression and Metastasis

Suping Ren, MD, PhD; Suhu Liu, MD, PhD; Paul Howell, Jr, BS; Yaguang Xi, MD; Steven A. Enkemann, MS, PhD; Jingfang Ju, PhD; Adam I. Riker, MD, FACS


Cancer Control. 2008;15(3):202-215. 

In This Article

Abstract and Introduction

Background: Recent technological advances in the analysis of the human genome have opened the door to improving our primitive understanding of the gene expression patterns in cancer. For the first time, we have an overview of the complexities of tumorigenesis and metastatic progression of cancer. The examination of the phenotypic and (epi)genetic changes in cutaneous melanoma has identified several genes deemed central to the development and progression of melanoma.
Methods: A review of the recent literature was performed to determine the role of array-based high-throughput gene expression analysis in understanding the specific genes involved as well as the pathways and the comparative gene expression patterns of primary and metastatic melanoma.
Results: Most studies utilizing gene microarray analysis and other whole genome approaches reveal a wide array of genes and expression patterns in human melanoma. Furthermore, several of the same genes have been found in comparative studies, with some studies attempting correlation with clinical outcome. Several genes have been identified as potential prognostic markers of tumor progression and overall clinical outcome.
Conclusions: High-throughput gene expression analysis has had a major impact in melanoma research. Several gene expression platforms have provided insight into the gene expression patterns in melanoma. Such data will provide the foundations for the future development of prognostic markers and improved targeted therapies for patients with melanoma.

Our simplistic understanding of the genetic basis for human disease has only recently begun to change as a result of the complete decoding of the human genome in 2001, led by the pioneering efforts of several research groups.[1,2,3,4] The unprecedented findings have enlightened and stimulated researchers worldwide to re-think our current paradigms of cancer development and metastatic progression in favor of shifting our approach to the level of gene function and regulation. It is compelling to think of the amazing technological advances that have occurred over the last 10 years,with such advances highlighting the sheer beauty, complexity, and intricate nature of the human genome and how it relates to the development of human malignant transformation. Indeed, we are on the first word of the first page of a very long novel.

Over the past decade, microarray-based high-throughput gene expression analysis of cancer has come to the forefront of cancer research, allowing us a comprehensive understanding of gene expression patterns involved in cancer initiation and progression. Since the absolute number of cases of primary cutaneous melanoma (PCM) is increasing at an astounding rate, researchers worldwide have refocused their efforts on trying to understand the genetic basis for the malignant transformation of this deadly disease.[5] The specific genes involved in this transformation process and subsequent progression of melanoma have not been fully described.[6,7,8,9,10,11]

There is ample evidence supportive of a strong correlation between the thickness of the PCM and the metastatic capacity of spreading either via the draining lymphatic channels or hematogenously.[12,13] Once melanoma has metastasized by either route, the overall survival for patients greatly diminishes.[14,15] Whereas patients with thin primary tumors are usually cured with the appropriate surgical resection, patients diagnosed with metastatic melanoma (MM) have a poor prognosis, with 6 out of every 7 skin cancer deaths ultimately due to MM.[5,16,17] Most patients with advanced disease do not respond to currently available therapies, thereby necessitating a greater need for the development of more effective treatments. In order to do so,we will need to vastly improve our current understanding of the molecular, genetic, immunologic, and cellular events that are intertwined with gene function and regulation as they relate to the malignant transformation of normal human epidermal melanocytes (NHEM) to a PCM and subsequently to metastatic disease.


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