Genomic Classification of Cutaneous Melanoma

The Cancer Genome Atlas Network

Research output: Contribution to journalArticle

969 Citations (Scopus)

Abstract

Summary We describe the landscape of genomic alterations in cutaneous melanomas through DNA, RNA, and protein-based analysis of 333 primary and/or metastatic melanomas from 331 patients. We establish a framework for genomic classification into one of four subtypes based on the pattern of the most prevalent significantly mutated genes: mutant BRAF, mutant RAS, mutant NF1, and Triple-WT (wild-type). Integrative analysis reveals enrichment of KIT mutations and focal amplifications and complex structural rearrangements as a feature of the Triple-WT subtype. We found no significant outcome correlation with genomic classification, but samples assigned a transcriptomic subclass enriched for immune gene expression associated with lymphocyte infiltrate on pathology review and high LCK protein expression, a T cell marker, were associated with improved patient survival. This clinicopathological and multi-dimensional analysis suggests that the prognosis of melanoma patients with regional metastases is influenced by tumor stroma immunobiology, offering insights to further personalize therapeutic decision-making.

Original languageEnglish (US)
Pages (from-to)1681-1696
Number of pages16
JournalCell
Volume161
Issue number7
DOIs
StatePublished - Jun 20 2015
Externally publishedYes

Fingerprint

Melanoma
Skin
T-cells
Lymphocytes
Pathology
Gene expression
Amplification
Tumors
Proteins
Genes
Decision making
RNA
DNA
Decision Making
Neoplasm Metastasis
T-Lymphocytes
Gene Expression
Mutation
Survival
Neoplasms

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

The Cancer Genome Atlas Network (2015). Genomic Classification of Cutaneous Melanoma. Cell, 161(7), 1681-1696. https://doi.org/10.1016/j.cell.2015.05.044

Genomic Classification of Cutaneous Melanoma. / The Cancer Genome Atlas Network.

In: Cell, Vol. 161, No. 7, 20.06.2015, p. 1681-1696.

Research output: Contribution to journalArticle

The Cancer Genome Atlas Network 2015, 'Genomic Classification of Cutaneous Melanoma', Cell, vol. 161, no. 7, pp. 1681-1696. https://doi.org/10.1016/j.cell.2015.05.044
The Cancer Genome Atlas Network. Genomic Classification of Cutaneous Melanoma. Cell. 2015 Jun 20;161(7):1681-1696. https://doi.org/10.1016/j.cell.2015.05.044
The Cancer Genome Atlas Network. / Genomic Classification of Cutaneous Melanoma. In: Cell. 2015 ; Vol. 161, No. 7. pp. 1681-1696.
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abstract = "Summary We describe the landscape of genomic alterations in cutaneous melanomas through DNA, RNA, and protein-based analysis of 333 primary and/or metastatic melanomas from 331 patients. We establish a framework for genomic classification into one of four subtypes based on the pattern of the most prevalent significantly mutated genes: mutant BRAF, mutant RAS, mutant NF1, and Triple-WT (wild-type). Integrative analysis reveals enrichment of KIT mutations and focal amplifications and complex structural rearrangements as a feature of the Triple-WT subtype. We found no significant outcome correlation with genomic classification, but samples assigned a transcriptomic subclass enriched for immune gene expression associated with lymphocyte infiltrate on pathology review and high LCK protein expression, a T cell marker, were associated with improved patient survival. This clinicopathological and multi-dimensional analysis suggests that the prognosis of melanoma patients with regional metastases is influenced by tumor stroma immunobiology, offering insights to further personalize therapeutic decision-making.",
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N2 - Summary We describe the landscape of genomic alterations in cutaneous melanomas through DNA, RNA, and protein-based analysis of 333 primary and/or metastatic melanomas from 331 patients. We establish a framework for genomic classification into one of four subtypes based on the pattern of the most prevalent significantly mutated genes: mutant BRAF, mutant RAS, mutant NF1, and Triple-WT (wild-type). Integrative analysis reveals enrichment of KIT mutations and focal amplifications and complex structural rearrangements as a feature of the Triple-WT subtype. We found no significant outcome correlation with genomic classification, but samples assigned a transcriptomic subclass enriched for immune gene expression associated with lymphocyte infiltrate on pathology review and high LCK protein expression, a T cell marker, were associated with improved patient survival. This clinicopathological and multi-dimensional analysis suggests that the prognosis of melanoma patients with regional metastases is influenced by tumor stroma immunobiology, offering insights to further personalize therapeutic decision-making.

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