Genomic landscape of cutaneous T cell lymphoma

Jaehyuk Choi; Gerald Goh; Trent Walradt; Bok S. Hong; Christopher G. Bunick; Kan Chen; Robert D. Bjornson; Yaakov Maman; Tiffany Wang; Jesse Tordoff; Kacie Carlson; John D. Overton; Kristina J. Liu; Julia M. Lewis; Lesley Devine; Lisa Barbarotta; Francine M. Foss; Antonio Subtil; Eric C. Vonderheid; Richard L. Edelson; David G. Schatz; Titus J. Boggon; Michael Girardi; Richard P. Lifton

doi:10.1038/ng.3356

Genomic landscape of cutaneous T cell lymphoma

Jaehyuk Choi, Gerald Goh, Trent Walradt, Bok S. Hong, Christopher G. Bunick, Kan Chen, Robert D. Bjornson, Yaakov Maman, Tiffany Wang, Jesse Tordoff, Kacie Carlson, John D. Overton, Kristina J. Liu, Julia M. Lewis, Lesley Devine, Lisa Barbarotta, Francine M. Foss, Antonio Subtil, Eric C. Vonderheid, Richard L. EdelsonDavid G. Schatz, Titus J. Boggon, Michael Girardi, Richard P. Lifton

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133 Scopus citations

Abstract

Cutaneous T cell lymphoma (CTCL) is a non-Hodgkin lymphoma of skin-homing T lymphocytes. We performed exome and whole-genome DNA sequencing and RNA sequencing on purified CTCL and matched normal cells. The results implicate mutations in 17 genes in CTCL pathogenesis, including genes involved in T cell activation and apoptosis, NF-Î° B signaling, chromatin remodeling and DNA damage response. CTCL is distinctive in that somatic copy number variants (SCNVs) comprise 92% of all driver mutations (mean of 11.8 pathogenic SCNVs versus 1.0 somatic single-nucleotide variant per CTCL). These findings have implications for new therapeutics.

Original language	English
Pages (from-to)	1011-1019
Number of pages	9
Journal	Nature Genetics
Volume	47
Issue number	9
DOIs	https://doi.org/10.1038/ng.3356
State	Published - 27 Aug 2015
Externally published	Yes

Bibliographical note

Funding Information:
We gratefully acknowledge the participation of the patients who made this research possible. We are grateful to I. Tikhonova and the staff of the Yale Center for Genome Analysis for their expert production of DNA and RNA sequence. Work was supported by the Dermatology Foundation and the Yale Specialized Program of Research Excellence (SPORE) in Skin Cancer Career Development Award (J.C.);. the Yale SPORE in Skin Cancer, P50 CA121974 (T.J.B.); the Agency for Science, Technology and Research, Singapore (G.G.); and US National Institutes of Health (NIH) grant RO1 CA102703 (M.G.). D.G.S. and R.P.L. are investigators of the Howard Hughes Medical Institute.

Publisher Copyright:
© 2015 Nature America, Inc. All rights reserved.

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Choi, J., Goh, G., Walradt, T., Hong, B. S., Bunick, C. G., Chen, K., Bjornson, R. D., Maman, Y., Wang, T., Tordoff, J., Carlson, K., Overton, J. D., Liu, K. J., Lewis, J. M., Devine, L., Barbarotta, L., Foss, F. M., Subtil, A., Vonderheid, E. C., ... Lifton, R. P. (2015). Genomic landscape of cutaneous T cell lymphoma. Nature Genetics, 47(9), 1011-1019. https://doi.org/10.1038/ng.3356

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title = "Genomic landscape of cutaneous T cell lymphoma",

abstract = "Cutaneous T cell lymphoma (CTCL) is a non-Hodgkin lymphoma of skin-homing T lymphocytes. We performed exome and whole-genome DNA sequencing and RNA sequencing on purified CTCL and matched normal cells. The results implicate mutations in 17 genes in CTCL pathogenesis, including genes involved in T cell activation and apoptosis, NF-{\^I}° B signaling, chromatin remodeling and DNA damage response. CTCL is distinctive in that somatic copy number variants (SCNVs) comprise 92% of all driver mutations (mean of 11.8 pathogenic SCNVs versus 1.0 somatic single-nucleotide variant per CTCL). These findings have implications for new therapeutics.",

author = "Jaehyuk Choi and Gerald Goh and Trent Walradt and Hong, {Bok S.} and Bunick, {Christopher G.} and Kan Chen and Bjornson, {Robert D.} and Yaakov Maman and Tiffany Wang and Jesse Tordoff and Kacie Carlson and Overton, {John D.} and Liu, {Kristina J.} and Lewis, {Julia M.} and Lesley Devine and Lisa Barbarotta and Foss, {Francine M.} and Antonio Subtil and Vonderheid, {Eric C.} and Edelson, {Richard L.} and Schatz, {David G.} and Boggon, {Titus J.} and Michael Girardi and Lifton, {Richard P.}",

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Choi, J, Goh, G, Walradt, T, Hong, BS, Bunick, CG, Chen, K, Bjornson, RD, Maman, Y, Wang, T, Tordoff, J, Carlson, K, Overton, JD, Liu, KJ, Lewis, JM, Devine, L, Barbarotta, L, Foss, FM, Subtil, A, Vonderheid, EC, Edelson, RL, Schatz, DG, Boggon, TJ, Girardi, M & Lifton, RP 2015, 'Genomic landscape of cutaneous T cell lymphoma', Nature Genetics, vol. 47, no. 9, pp. 1011-1019. https://doi.org/10.1038/ng.3356

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AU - Vonderheid, Eric C.

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Genomic landscape of cutaneous T cell lymphoma

Abstract

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