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Genome Res. 2017 Apr;27(4):524-532. doi: 10.1101/gr.213348.116.

Integrated genomic analyses reveal frequent TERT aberrations in acral melanoma.

Author information

1
Translational Genomics Research Institute, Phoenix, Arizona 85004, USA.
2
Mayo Clinic, Scottsdale, Arizona 85259, USA.
3
University of Arizona, College of Pharmacy, Tucson, Arizona 85721, USA.
4
Vanderbilt University Medical Center, Nashville, Tennessee 37232, USA.
5
Memorial Sloan-Kettering Cancer Center, New York, New York 10065, USA.
6
Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul 135-710, Korea.
7
Northwestern University, Robert H. Lurie Comprehensive Cancer Center, Chicago, Illinois 60611, USA.

Abstract

Genomic analyses of cutaneous melanoma (CM) have yielded biological and therapeutic insights, but understanding of non-ultraviolet (UV)-derived CMs remains limited. Deeper analysis of acral lentiginous melanoma (ALM), a rare sun-shielded melanoma subtype associated with worse survival than CM, is needed to delineate non-UV oncogenic mechanisms. We thus performed comprehensive genomic and transcriptomic analysis of 34 ALM patients. Unlike CM, somatic alterations were dominated by structural variation and absence of UV-derived mutation signatures. Only 38% of patients demonstrated driver BRAF/NRAS/NF1 mutations. In contrast with CM, we observed PAK1 copy gains in 15% of patients, and somatic TERT translocations, copy gains, and missense and promoter mutations, or germline events, in 41% of patients. We further show that in vitro TERT inhibition has cytotoxic effects on primary ALM cells. These findings provide insight into the role of TERT in ALM tumorigenesis and reveal preliminary evidence that TERT inhibition represents a potential therapeutic strategy in ALM.

PMID:
28373299
PMCID:
PMC5378171
DOI:
10.1101/gr.213348.116
[Indexed for MEDLINE]
Free PMC Article

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