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

Research output: Contribution to journal › Article › peer-review

361 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 - Sep 2015
Externally published	Yes

Bibliographical note

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

Funding

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.

Funders	Funder number
Agency for Science, Technology and Research, Singapore
National Institutes of Health	RO1 CA102703
National Cancer Institute	P50CA121974
Dermatology Foundation	P50 CA121974

Access to Document

10.1038/ng.3356

Cite this

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

@article{fb7f89399ec1435e9301a36a36852ef9,

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.}",

year = "2015",

month = sep,

doi = "10.1038/ng.3356",

language = "אנגלית",

volume = "47",

pages = "1011--1019",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "9",

}

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

TY - JOUR

T1 - Genomic landscape of cutaneous T cell lymphoma

AU - Choi, Jaehyuk

AU - Goh, Gerald

AU - Walradt, Trent

AU - Hong, Bok S.

AU - Bunick, Christopher G.

AU - Chen, Kan

AU - Bjornson, Robert D.

AU - Maman, Yaakov

AU - Wang, Tiffany

AU - Tordoff, Jesse

AU - Carlson, Kacie

AU - Overton, John D.

AU - Liu, Kristina J.

AU - Lewis, Julia M.

AU - Devine, Lesley

AU - Barbarotta, Lisa

AU - Foss, Francine M.

AU - Subtil, Antonio

AU - Vonderheid, Eric C.

AU - Edelson, Richard L.

AU - Schatz, David G.

AU - Boggon, Titus J.

AU - Girardi, Michael

AU - Lifton, Richard P.

PY - 2015/9

Y1 - 2015/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84940585634&partnerID=8YFLogxK

U2 - 10.1038/ng.3356

DO - 10.1038/ng.3356

M3 - ???researchoutput.researchoutputtypes.contributiontojournal.article???

C2 - 26192916

AN - SCOPUS:84940585634

SN - 1061-4036

VL - 47

SP - 1011

EP - 1019

JO - Nature Genetics

JF - Nature Genetics

IS - 9

ER -

Genomic landscape of cutaneous T cell lymphoma

Abstract

Bibliographical note

Funding

Access to Document

Other files and links

Fingerprint

Cite this