Using global gene expression to discriminate thin melanomas with poor outcomes
Most melanomas present as thin lesions (≤1.0 mm) with a good prognosis; however, a small percentage of patients with thin lesions experience recurrence or metastasis. The aim of our study was to identify a distinct pattern of gene expression within thin melanomas known to have eventually metastasize...
Main Authors: | , , , , , , , , , |
---|---|
Format: | Article |
Language: | English |
Published: |
Taylor & Francis Group
2017-01-01
|
Series: | Molecular & Cellular Oncology |
Subjects: | |
Online Access: | http://dx.doi.org/10.1080/23723556.2016.1253527 |
_version_ | 1797677229753237504 |
---|---|
author | Zachary Hothem Andrew Bayci Bryan J. Thibodeau Billie E. Ketelsen Laura E. Fortier Alison F. Uzieblo Diane Cosner Kristin Totoraitis Richard D. Keidan George D. Wilson |
author_facet | Zachary Hothem Andrew Bayci Bryan J. Thibodeau Billie E. Ketelsen Laura E. Fortier Alison F. Uzieblo Diane Cosner Kristin Totoraitis Richard D. Keidan George D. Wilson |
author_sort | Zachary Hothem |
collection | DOAJ |
description | Most melanomas present as thin lesions (≤1.0 mm) with a good prognosis; however, a small percentage of patients with thin lesions experience recurrence or metastasis. The aim of our study was to identify a distinct pattern of gene expression within thin melanomas known to have eventually metastasized to regional lymph nodes or distant sites compared with those that followed the typical course with good response to wide local excision alone. Patients who were disease-free for a minimum of 10 y served as controls (n = 10) to the experimental group who developed metastasis (n = 9). Laser capture microdissection was used to specifically isolate cancer cells from formalin-fixed paraffin-embedded tissue with subsequent gene expression analysis on Affymetrix Human Transcriptome Array 2.0 Arrays. Although gene expression differences were observed between the patients with thin melanoma with poor clinical outcome and those with good clinical outcome, neither the number of genes nor the magnitude of the fold difference was very substantial or significant. Cluster analysis with this subset of genes could definitively separate a subset of the poor responders from the good responders, but there remained a mixed group of tumors that could not be predicted from gene expression alone. Pathway analysis identified cellular processes that were regulated based on the response, including categories commonly associated with melanoma progression. Ultimately, we concluded that there were very few differences between these groups. Future research will be required and investigation of the mutational landscape may be another strategy to uncover genomic changes that drive recurrence and metastasis in thin melanoma. |
first_indexed | 2024-03-11T22:42:02Z |
format | Article |
id | doaj.art-a05c83b23e0b421a99e2dcc8c9d4580f |
institution | Directory Open Access Journal |
issn | 2372-3556 |
language | English |
last_indexed | 2024-03-11T22:42:02Z |
publishDate | 2017-01-01 |
publisher | Taylor & Francis Group |
record_format | Article |
series | Molecular & Cellular Oncology |
spelling | doaj.art-a05c83b23e0b421a99e2dcc8c9d4580f2023-09-22T09:10:57ZengTaylor & Francis GroupMolecular & Cellular Oncology2372-35562017-01-014110.1080/23723556.2016.12535271253527Using global gene expression to discriminate thin melanomas with poor outcomesZachary Hothem0Andrew Bayci1Bryan J. Thibodeau2Billie E. Ketelsen3Laura E. Fortier4Alison F. Uzieblo5Diane Cosner6Kristin Totoraitis7Richard D. Keidan8George D. Wilson9William Beaumont HospitalWilliam Beaumont HospitalWilliam Beaumont HospitalWilliam Beaumont HospitalWilliam Beaumont HospitalWilliam Beaumont HospitalWilliam Beaumont HospitalOakland University William Beaumont School of MedicineWilliam Beaumont HospitalWilliam Beaumont HospitalMost melanomas present as thin lesions (≤1.0 mm) with a good prognosis; however, a small percentage of patients with thin lesions experience recurrence or metastasis. The aim of our study was to identify a distinct pattern of gene expression within thin melanomas known to have eventually metastasized to regional lymph nodes or distant sites compared with those that followed the typical course with good response to wide local excision alone. Patients who were disease-free for a minimum of 10 y served as controls (n = 10) to the experimental group who developed metastasis (n = 9). Laser capture microdissection was used to specifically isolate cancer cells from formalin-fixed paraffin-embedded tissue with subsequent gene expression analysis on Affymetrix Human Transcriptome Array 2.0 Arrays. Although gene expression differences were observed between the patients with thin melanoma with poor clinical outcome and those with good clinical outcome, neither the number of genes nor the magnitude of the fold difference was very substantial or significant. Cluster analysis with this subset of genes could definitively separate a subset of the poor responders from the good responders, but there remained a mixed group of tumors that could not be predicted from gene expression alone. Pathway analysis identified cellular processes that were regulated based on the response, including categories commonly associated with melanoma progression. Ultimately, we concluded that there were very few differences between these groups. Future research will be required and investigation of the mutational landscape may be another strategy to uncover genomic changes that drive recurrence and metastasis in thin melanoma.http://dx.doi.org/10.1080/23723556.2016.1253527gene expressionmelanomamicroarraythin melanomasurgical response |
spellingShingle | Zachary Hothem Andrew Bayci Bryan J. Thibodeau Billie E. Ketelsen Laura E. Fortier Alison F. Uzieblo Diane Cosner Kristin Totoraitis Richard D. Keidan George D. Wilson Using global gene expression to discriminate thin melanomas with poor outcomes Molecular & Cellular Oncology gene expression melanoma microarray thin melanoma surgical response |
title | Using global gene expression to discriminate thin melanomas with poor outcomes |
title_full | Using global gene expression to discriminate thin melanomas with poor outcomes |
title_fullStr | Using global gene expression to discriminate thin melanomas with poor outcomes |
title_full_unstemmed | Using global gene expression to discriminate thin melanomas with poor outcomes |
title_short | Using global gene expression to discriminate thin melanomas with poor outcomes |
title_sort | using global gene expression to discriminate thin melanomas with poor outcomes |
topic | gene expression melanoma microarray thin melanoma surgical response |
url | http://dx.doi.org/10.1080/23723556.2016.1253527 |
work_keys_str_mv | AT zacharyhothem usingglobalgeneexpressiontodiscriminatethinmelanomaswithpooroutcomes AT andrewbayci usingglobalgeneexpressiontodiscriminatethinmelanomaswithpooroutcomes AT bryanjthibodeau usingglobalgeneexpressiontodiscriminatethinmelanomaswithpooroutcomes AT billieeketelsen usingglobalgeneexpressiontodiscriminatethinmelanomaswithpooroutcomes AT lauraefortier usingglobalgeneexpressiontodiscriminatethinmelanomaswithpooroutcomes AT alisonfuzieblo usingglobalgeneexpressiontodiscriminatethinmelanomaswithpooroutcomes AT dianecosner usingglobalgeneexpressiontodiscriminatethinmelanomaswithpooroutcomes AT kristintotoraitis usingglobalgeneexpressiontodiscriminatethinmelanomaswithpooroutcomes AT richarddkeidan usingglobalgeneexpressiontodiscriminatethinmelanomaswithpooroutcomes AT georgedwilson usingglobalgeneexpressiontodiscriminatethinmelanomaswithpooroutcomes |