Epigenetic dysregulation of novel candidate genes in melanoma
type: CreativeWork
description: Cutaneous melanoma (CM) is an aggressive neoplastic disorder of melanocytes accounting for 4% of skin cancers, but over 75% of skin cancer-related deaths. The outlook for advanced melanoma is typically poor, particularly for patients with distant and/or visceral metastatic disease. Although new melanoma therapies including vemurafenib and ipilimumab confer significant clinical benefit, accumulating evidence suggests that they are less effective when tumour load is high and patient performance status poor, as is often the case in advanced disease. New strategies for the early detection of sub-clinical relapsed and/or metastatic disease are therefore urgently required. Development of such biomarkers, combining sensitivity and specificity, would allow the deployment of these treatments when tumour volume is low thereby maximising anti-melanoma efficacy. Cancer-associated gene promoter methylation is recognized as an important mechanism in tumour initiation and progression. Exploring the epigenetic profiles of melanoma will lead to the generation of new strategies for molecular subtyping, discovery of diagnostic and prognostic biomarkers and development of novel therapeutic targets. In the present study, I have identified a panel of promising epigenetic melanoma biomarkers by exploiting both a systematic approach and candidate gene approach. Biomarkers TFPI2 and P4HA3 showed a high frequency and high level of methylation in melanoma cell lines. Significantly increased methylation in melanoma suggests a role for TFPI2 and P4HA3 as epigenetic biomarkers that can potentially predict poor prognosis of melanoma. Furthermore, in my work a highly significant correlation has been established between detection of methylated genomic DNA of TFPI2 and P4HA3 in melanoma patients’ sera and metastatic disease. This implies potential clinical utility for TFPI2 and P4HA3 as serum biomarkers for the detection of metastatic melanoma. In contrast, the presence of NT5E and DUSP2 methylation…
abstract: Cutaneous melanoma (CM) is an aggressive neoplastic disorder of melanocytes accounting for 4% of skin cancers, but over 75% of skin cancer-related deaths. The outlook for advanced melanoma is typically poor, particularly for patients with distant and/or visceral metastatic disease. Although new melanoma therapies including vemurafenib and ipilimumab confer significant clinical benefit, accumulating evidence suggests that they are less effective when tumour load is high and patient performance status poor, as is often the case in advanced disease. New strategies for the early detection of sub-clinical relapsed and/or metastatic disease are therefore urgently required. Development of such biomarkers, combining sensitivity and specificity, would allow the deployment of these treatments when tumour volume is low thereby maximising anti-melanoma efficacy. Cancer-associated gene promoter methylation is recognized as an important mechanism in tumour initiation and progression. Exploring the epigenetic profiles of melanoma will lead to the generation of new strategies for molecular subtyping, discovery of diagnostic and prognostic biomarkers and development of novel therapeutic targets. In the present study, I have identified a panel of promising epigenetic melanoma biomarkers by exploiting both a systematic approach and candidate gene approach. Biomarkers TFPI2 and P4HA3 showed a high frequency and high level of methylation in melanoma cell lines. Significantly increased methylation in melanoma suggests a role for TFPI2 and P4HA3 as epigenetic biomarkers that can potentially predict poor prognosis of melanoma. Furthermore, in my work a highly significant correlation has been established between detection of methylated genomic DNA of TFPI2 and P4HA3 in melanoma patients’ sera and metastatic disease. This implies potential clinical utility for TFPI2 and P4HA3 as serum biomarkers for the detection of metastatic melanoma. In contrast, the presence of NT5E and DUSP2 methylation…
author: Wang, Hexiao
language: eng
date published: 2013
date modified: 2026-07-24T02:07:46Z
provider: University of Dundee
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: University of Dundee