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Independent replication of a melanoma subtype gene signature and evaluation of its prognostic value and biological correlates in a population cohort.

Nsengimana, Jérémie; Laye, Jon; Filia, Anastasia; Walker, Christy; Jewell, Rosalyn; Van den Oord, Joost J; Wolter, Pascal; Patel, Poulam; Sucker, Antje and Schadendorf, Dirk, et al. (2015) In Oncotarget 6(13). p.11683-11693
Abstract
Development and validation of robust molecular biomarkers has so far been limited in melanoma research. In this paper we used a large population-based cohort to replicate two published gene signatures for melanoma classification. We assessed the signatures prognostic value and explored their biological significance by correlating them with factors known to be associated with survival (vitamin D) or etiological routes (nevi, sun sensitivity and telomere length). Genomewide microarray gene expressions were profiled in 300 archived tumors (224 primaries, 76 secondaries). The two gene signatures classified up to 96% of our samples and showed strong correlation with melanoma specific survival (P=3x10-4), Breslow thickness (P=5x10-10),... (More)
Development and validation of robust molecular biomarkers has so far been limited in melanoma research. In this paper we used a large population-based cohort to replicate two published gene signatures for melanoma classification. We assessed the signatures prognostic value and explored their biological significance by correlating them with factors known to be associated with survival (vitamin D) or etiological routes (nevi, sun sensitivity and telomere length). Genomewide microarray gene expressions were profiled in 300 archived tumors (224 primaries, 76 secondaries). The two gene signatures classified up to 96% of our samples and showed strong correlation with melanoma specific survival (P=3x10-4), Breslow thickness (P=5x10-10), ulceration (P=9.x10-8) and mitotic rate (P=3x10-7), adding prognostic value over AJCC stage (adjusted hazard ratio 1.79, 95%CI 1.13-2.83), as previously reported. Furthermore, molecular subtypes were associated with season-adjusted serum vitamin D at diagnosis (P=0.04) and genetically predicted telomere length (P=0.03). Specifically, molecular high-grade tumors were more frequent in patients with lower vitamin D levels whereas high immune tumors came from patients with predicted shorter telomeres. Our data confirm the utility of molecular biomarkers in melanoma prognostic estimation using tiny archived specimens and shed light on biological mechanisms likely to impact on cancer initiation and progression. (Less)
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Oncotarget
volume
6
issue
13
pages
11683 - 11693
publisher
Impact Journals, LLC
external identifiers
  • pmid:25871393
  • wos:000359006400078
  • scopus:84929630738
ISSN
1949-2553
DOI
10.18632/oncotarget.3549
language
English
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yes
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022140d3-dc95-4ce4-9760-5278f3338679 (old id 5341931)
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http://www.ncbi.nlm.nih.gov/pubmed/25871393?dopt=Abstract
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2015-05-05 20:14:06
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2017-07-23 04:24:28
@article{022140d3-dc95-4ce4-9760-5278f3338679,
  abstract     = {Development and validation of robust molecular biomarkers has so far been limited in melanoma research. In this paper we used a large population-based cohort to replicate two published gene signatures for melanoma classification. We assessed the signatures prognostic value and explored their biological significance by correlating them with factors known to be associated with survival (vitamin D) or etiological routes (nevi, sun sensitivity and telomere length). Genomewide microarray gene expressions were profiled in 300 archived tumors (224 primaries, 76 secondaries). The two gene signatures classified up to 96% of our samples and showed strong correlation with melanoma specific survival (P=3x10-4), Breslow thickness (P=5x10-10), ulceration (P=9.x10-8) and mitotic rate (P=3x10-7), adding prognostic value over AJCC stage (adjusted hazard ratio 1.79, 95%CI 1.13-2.83), as previously reported. Furthermore, molecular subtypes were associated with season-adjusted serum vitamin D at diagnosis (P=0.04) and genetically predicted telomere length (P=0.03). Specifically, molecular high-grade tumors were more frequent in patients with lower vitamin D levels whereas high immune tumors came from patients with predicted shorter telomeres. Our data confirm the utility of molecular biomarkers in melanoma prognostic estimation using tiny archived specimens and shed light on biological mechanisms likely to impact on cancer initiation and progression.},
  author       = {Nsengimana, Jérémie and Laye, Jon and Filia, Anastasia and Walker, Christy and Jewell, Rosalyn and Van den Oord, Joost J and Wolter, Pascal and Patel, Poulam and Sucker, Antje and Schadendorf, Dirk and Jönsson, Göran B and Bishop, D Timothy and Newton-Bishop, Julia},
  issn         = {1949-2553},
  language     = {eng},
  number       = {13},
  pages        = {11683--11693},
  publisher    = {Impact Journals, LLC},
  series       = {Oncotarget},
  title        = {Independent replication of a melanoma subtype gene signature and evaluation of its prognostic value and biological correlates in a population cohort.},
  url          = {http://dx.doi.org/10.18632/oncotarget.3549},
  volume       = {6},
  year         = {2015},
}