Integrated genomic analyses reveal frequent TERT aberrations in acral melanoma Journal Article

Authors: Liang, W. S.; Hendricks, W.; Kiefer, J.; Schmidt, J.; Sekar, S.; Carpten, J.; Craig, D. W.; Adkins, J.; Cuyugan, L.; Manojlovic, Z.; Halperin, R. F.; Helland, A.; Nasser, S.; Legendre, C.; Hurley, L. H.; Sivaprakasam, K.; Johnson, D. B.; Crandall, H.; Busam, K. J.; Zismann, V.; Deluca, V.; Lee, J.; Sekulic, A.; Ariyan, C. E.; Sosman, J.; Trent, J.
Article Title: Integrated genomic analyses reveal frequent TERT aberrations in acral melanoma
Abstract: Genomic analyses of cutaneous melanoma (CM) have yielded biological and therapeutic insights, but understanding of nonultraviolet (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. ©2017 Liang et al.
Journal Title: Genome Research
Volume: 27
Issue: 4
ISSN: 1088-9051
Publisher: Cold Spring Harbor Laboratory Press  
Date Published: 2017-04-01
Start Page: 524
End Page: 532
Language: English
DOI: 10.1101/gr.213348.116
PROVIDER: scopus
PMCID: PMC5378171
PUBMED: 28373299
Notes: Article -- Export Date: 2 May 2017 -- Source: Scopus
Citation Impact
MSK Authors
  1. Charlotte Eielson Ariyan
    132 Ariyan
  2. Klaus J Busam
    650 Busam