Genome-Wide Analysis of Gene and Protein Expression of Dysplastic Naevus Cells

Cutaneous melanoma, a type of skin tumor originating from melanocytes, often develops from premalignant naevoid lesions via a gradual transformation process driven by an accumulation of (epi)genetic lesions. These dysplastic naevi display altered morphology and often proliferation of melanocytes. Ad...

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Main Authors: Linda Gao, Frans A. van Nieuwpoort, Jacoba J. Out-Luiting, Paul J. Hensbergen, Femke A. de Snoo, Wilma Bergman, Remco van Doorn, Nelleke A. Gruis
Format: Article
Language:English
Published: Wiley 2012-01-01
Series:Journal of Skin Cancer
Online Access:http://dx.doi.org/10.1155/2012/981308
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author Linda Gao
Frans A. van Nieuwpoort
Jacoba J. Out-Luiting
Paul J. Hensbergen
Femke A. de Snoo
Wilma Bergman
Remco van Doorn
Nelleke A. Gruis
author_facet Linda Gao
Frans A. van Nieuwpoort
Jacoba J. Out-Luiting
Paul J. Hensbergen
Femke A. de Snoo
Wilma Bergman
Remco van Doorn
Nelleke A. Gruis
author_sort Linda Gao
collection DOAJ
description Cutaneous melanoma, a type of skin tumor originating from melanocytes, often develops from premalignant naevoid lesions via a gradual transformation process driven by an accumulation of (epi)genetic lesions. These dysplastic naevi display altered morphology and often proliferation of melanocytes. Additionally, melanocytes in dysplastic naevi show structural mitochondrial and melanosomal alterations and have elevated reactive oxygen species (ROS) levels. For this study we performed genome-wide expression and proteomic analysis of melanocytes from dysplastic naevus (DNMC) and adjacent normal skin (MC) from 18 patients. Whole genome expression profiles of the DNMC and MC of each individual patient subjected to GO-based comparative statistical analysis yielded significantly differentially expressed GO classes including “organellar ribosome,” “mitochondrial ribosome,” “hydrogen ion transporter activity,” and “prefoldin complex.” Validation of 5 genes from these top GO classes revealed a heterogeneous differential expression pattern. Proteomic analysis demonstrated differentially expressed proteins in DNMC that are involved in cellular metabolism, detoxification, and cytoskeletal organization processes, such as GTP-binding Rho-like protein CDC42, glutathione-S-transferase omega-1 and prolyl 4-hydroxylase. Collectively these results point to deregulation of cellular processes, such as metabolism and protein synthesis, consistent with the observed elevated oxidative stress levels in DNMC potentially resulting in oxidative DNA damage in these cells.
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spelling doaj-art-e2bc4ce6cc3a4aa389c91b836c3292e72025-08-20T03:21:07ZengWileyJournal of Skin Cancer2090-29052090-29132012-01-01201210.1155/2012/981308981308Genome-Wide Analysis of Gene and Protein Expression of Dysplastic Naevus CellsLinda Gao0Frans A. van Nieuwpoort1Jacoba J. Out-Luiting2Paul J. Hensbergen3Femke A. de Snoo4Wilma Bergman5Remco van Doorn6Nelleke A. Gruis7Department of Dermatology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The NetherlandsDepartment of Dermatology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The NetherlandsDepartment of Dermatology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The NetherlandsDepartment of Parasitology, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The NetherlandsCenter for Human and Clinical Genetics, Leiden University Medical Center, Albinusdreef 2, 2300 RC Leiden, The NetherlandsDepartment of Dermatology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The NetherlandsDepartment of Dermatology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The NetherlandsDepartment of Dermatology, Leiden University Medical Center, Einthovenweg 20, 2333 ZC Leiden, The NetherlandsCutaneous melanoma, a type of skin tumor originating from melanocytes, often develops from premalignant naevoid lesions via a gradual transformation process driven by an accumulation of (epi)genetic lesions. These dysplastic naevi display altered morphology and often proliferation of melanocytes. Additionally, melanocytes in dysplastic naevi show structural mitochondrial and melanosomal alterations and have elevated reactive oxygen species (ROS) levels. For this study we performed genome-wide expression and proteomic analysis of melanocytes from dysplastic naevus (DNMC) and adjacent normal skin (MC) from 18 patients. Whole genome expression profiles of the DNMC and MC of each individual patient subjected to GO-based comparative statistical analysis yielded significantly differentially expressed GO classes including “organellar ribosome,” “mitochondrial ribosome,” “hydrogen ion transporter activity,” and “prefoldin complex.” Validation of 5 genes from these top GO classes revealed a heterogeneous differential expression pattern. Proteomic analysis demonstrated differentially expressed proteins in DNMC that are involved in cellular metabolism, detoxification, and cytoskeletal organization processes, such as GTP-binding Rho-like protein CDC42, glutathione-S-transferase omega-1 and prolyl 4-hydroxylase. Collectively these results point to deregulation of cellular processes, such as metabolism and protein synthesis, consistent with the observed elevated oxidative stress levels in DNMC potentially resulting in oxidative DNA damage in these cells.http://dx.doi.org/10.1155/2012/981308
spellingShingle Linda Gao
Frans A. van Nieuwpoort
Jacoba J. Out-Luiting
Paul J. Hensbergen
Femke A. de Snoo
Wilma Bergman
Remco van Doorn
Nelleke A. Gruis
Genome-Wide Analysis of Gene and Protein Expression of Dysplastic Naevus Cells
Journal of Skin Cancer
title Genome-Wide Analysis of Gene and Protein Expression of Dysplastic Naevus Cells
title_full Genome-Wide Analysis of Gene and Protein Expression of Dysplastic Naevus Cells
title_fullStr Genome-Wide Analysis of Gene and Protein Expression of Dysplastic Naevus Cells
title_full_unstemmed Genome-Wide Analysis of Gene and Protein Expression of Dysplastic Naevus Cells
title_short Genome-Wide Analysis of Gene and Protein Expression of Dysplastic Naevus Cells
title_sort genome wide analysis of gene and protein expression of dysplastic naevus cells
url http://dx.doi.org/10.1155/2012/981308
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