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Molecular and Cellular Biology, Genetics

Abstract 3389: Integrated genomic analyses reveal frequent TERT aberrations in acral melanoma

Winnie S. Liang, William Hendricks, Jeffrey Kiefer, Jessica Schmidt, Shobana Sekar, John Carpten, David W. Craig, Jonathan Adkins, Lori Cuyugan, Zarko Manojlovic, Rebecca F. Halperin, Adrienne Helland, Sara Nasser, Christophe Legendre, Laurence H. Hurley, Karthigayini Sivaprakasam, Douglas B. Johnson, Holly Crandall, Klaus J. Busam, Victoria Zismann, Valerie De Luca, Jeeyun Lee, Aleksandar Sekulic, Charlotte E. Ariyan, Jeffrey Sosman and Jeffrey Trent
Winnie S. Liang
TGen (The Translational Genomics Research Institute), Phoenix, AZ;
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William Hendricks
TGen (The Translational Genomics Research Institute), Phoenix, AZ;
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Jeffrey Kiefer
TGen (The Translational Genomics Research Institute), Phoenix, AZ;
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Jessica Schmidt
Mayo Clinic, Scottsdale, AZ;
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Shobana Sekar
TGen (The Translational Genomics Research Institute), Phoenix, AZ;
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John Carpten
TGen (The Translational Genomics Research Institute), Phoenix, AZ;
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David W. Craig
TGen (The Translational Genomics Research Institute), Phoenix, AZ;
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Jonathan Adkins
TGen (The Translational Genomics Research Institute), Phoenix, AZ;
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Lori Cuyugan
TGen (The Translational Genomics Research Institute), Phoenix, AZ;
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Zarko Manojlovic
TGen (The Translational Genomics Research Institute), Phoenix, AZ;
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Rebecca F. Halperin
TGen (The Translational Genomics Research Institute), Phoenix, AZ;
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Adrienne Helland
TGen (The Translational Genomics Research Institute), Phoenix, AZ;
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Sara Nasser
TGen (The Translational Genomics Research Institute), Phoenix, AZ;
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Christophe Legendre
TGen (The Translational Genomics Research Institute), Phoenix, AZ;
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Laurence H. Hurley
University of Arizona, Tucson, AZ;
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Karthigayini Sivaprakasam
TGen (The Translational Genomics Research Institute), Phoenix, AZ;
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Douglas B. Johnson
Vanderbilt University Medical Center, Nashville, TN;
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Holly Crandall
Vanderbilt University Medical Center, Nashville, TN;
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Klaus J. Busam
Memorial Sloan-Kettering Cancer Center, New York, NY;
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Victoria Zismann
TGen (The Translational Genomics Research Institute), Phoenix, AZ;
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Valerie De Luca
TGen (The Translational Genomics Research Institute), Phoenix, AZ;
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Jeeyun Lee
Samsung Medical Center, Seoul, Democratic People's Republic of Korea;
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Aleksandar Sekulic
Mayo Clinic, Scottsdale, AZ;
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Charlotte E. Ariyan
Memorial Sloan-Kettering Cancer Center, New York, NY;
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Jeffrey Sosman
Northwestern University, Chicago, IL.
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Jeffrey Trent
TGen (The Translational Genomics Research Institute), Phoenix, AZ;
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DOI: 10.1158/1538-7445.AM2017-3389 Published July 2017
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Proceedings: AACR Annual Meeting 2017; April 1-5, 2017; Washington, DC

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. Contrasting 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.

Citation Format: Winnie S. Liang, William Hendricks, Jeffrey Kiefer, Jessica Schmidt, Shobana Sekar, John Carpten, David W. Craig, Jonathan Adkins, Lori Cuyugan, Zarko Manojlovic, Rebecca F. Halperin, Adrienne Helland, Sara Nasser, Christophe Legendre, Laurence H. Hurley, Karthigayini Sivaprakasam, Douglas B. Johnson, Holly Crandall, Klaus J. Busam, Victoria Zismann, Valerie De Luca, Jeeyun Lee, Aleksandar Sekulic, Charlotte E. Ariyan, Jeffrey Sosman, Jeffrey Trent. Integrated genomic analyses reveal frequent TERT aberrations in acral melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3389. doi:10.1158/1538-7445.AM2017-3389

  • ©2017 American Association for Cancer Research.
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Cancer Research: 77 (13 Supplement)
July 2017
Volume 77, Issue 13 Supplement
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Abstract 3389: Integrated genomic analyses reveal frequent TERT aberrations in acral melanoma
Winnie S. Liang, William Hendricks, Jeffrey Kiefer, Jessica Schmidt, Shobana Sekar, John Carpten, David W. Craig, Jonathan Adkins, Lori Cuyugan, Zarko Manojlovic, Rebecca F. Halperin, Adrienne Helland, Sara Nasser, Christophe Legendre, Laurence H. Hurley, Karthigayini Sivaprakasam, Douglas B. Johnson, Holly Crandall, Klaus J. Busam, Victoria Zismann, Valerie De Luca, Jeeyun Lee, Aleksandar Sekulic, Charlotte E. Ariyan, Jeffrey Sosman and Jeffrey Trent
Cancer Res July 1 2017 (77) (13 Supplement) 3389; DOI: 10.1158/1538-7445.AM2017-3389

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Abstract 3389: Integrated genomic analyses reveal frequent TERT aberrations in acral melanoma
Winnie S. Liang, William Hendricks, Jeffrey Kiefer, Jessica Schmidt, Shobana Sekar, John Carpten, David W. Craig, Jonathan Adkins, Lori Cuyugan, Zarko Manojlovic, Rebecca F. Halperin, Adrienne Helland, Sara Nasser, Christophe Legendre, Laurence H. Hurley, Karthigayini Sivaprakasam, Douglas B. Johnson, Holly Crandall, Klaus J. Busam, Victoria Zismann, Valerie De Luca, Jeeyun Lee, Aleksandar Sekulic, Charlotte E. Ariyan, Jeffrey Sosman and Jeffrey Trent
Cancer Res July 1 2017 (77) (13 Supplement) 3389; DOI: 10.1158/1538-7445.AM2017-3389
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