A targeted mutational landscape of angioimmunoblastic T-cell lymphoma

Oreofe Odejide; Oliver Weigert; Andrew A. Lane; Dan Toscano; Matthew A. Lunning; Nadja Kopp; Sunhee Kim; Diederik Van Bodegom; Sudha Bolla; Jonathan H. Schatz; Julie Teruya-Feldstein; Ephraim Hochberg; Abner Louissaint; David Dorfman; Kristen Stevenson; Scott J. Rodig; Pier Paolo Piccaluga; Eric Jacobsen; Stefano A. Pileri; Nancy L. Harris; Simone Ferrero; Giorgio Inghirami; Steven M. Horwitz; David M. Weinstock

doi:10.1182/blood-2013-10-531509

A targeted mutational landscape of angioimmunoblastic T-cell lymphoma

Oreofe Odejide
, Oliver Weigert
, Andrew A. Lane
, Dan Toscano
, Matthew A. Lunning
, Nadja Kopp
, Sunhee Kim
, Diederik Van Bodegom
, Sudha Bolla
, Jonathan H. Schatz
, Julie Teruya-Feldstein
, Ephraim Hochberg
, Abner Louissaint
, David Dorfman
, Kristen Stevenson
, Scott J. Rodig
, Pier Paolo Piccaluga
, Eric Jacobsen
, Stefano A. Pileri
, Nancy L. Harris

Simone Ferrero, Giorgio Inghirami, Steven M. Horwitz, David M. Weinstock

Medicine

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

366 Scopus citations

Abstract

The genetics of angioimmunoblastic T-cell lymphoma (AITL) are very poorly understood. We defined the mutational landscape of AITL across 219 genes in 85 cases from the United States and Europe. We identified ≥2 mutations in 34 genes, nearly all of which were not previously implicated in AITL. These included loss-of-function mutations in TP53 (n = 4), ETV6 (n = 3), CCND3 (n = 2), and EP300 (n = 5), as well as gain-of-function mutations in JAK2 (n = 2) and STAT3 (n = 4). TET2 was mutated in 65 (76%) AITLs, including 43 that harbored 2 or 3 TET2 mutations. DNMT3A mutations occurred in 28 (33%) AITLs; 100% of these also harbored TET2 mutations (P < .0001). Seventeen AITLs harbored IDH2 R172 substitutions, including 15 with TET2 mutations. In summary, AITL is characterized by high frequencies of overlapping mutations in epigenetic modifiers and targetable mutations in a subset of cases.

Original language	English (US)
Pages (from-to)	1293-1296
Number of pages	4
Journal	Blood
Volume	123
Issue number	9
DOIs	https://doi.org/10.1182/blood-2013-10-531509
State	Published - Feb 27 2014

ASJC Scopus subject areas

Biochemistry
Immunology
Hematology
Cell Biology

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Odejide, O., Weigert, O., Lane, A. A., Toscano, D., Lunning, M. A., Kopp, N., Kim, S., Van Bodegom, D., Bolla, S., Schatz, J. H., Teruya-Feldstein, J., Hochberg, E., Louissaint, A., Dorfman, D., Stevenson, K., Rodig, S. J., Piccaluga, P. P., Jacobsen, E., Pileri, S. A., ... Weinstock, D. M. (2014). A targeted mutational landscape of angioimmunoblastic T-cell lymphoma. Blood, 123(9), 1293-1296. https://doi.org/10.1182/blood-2013-10-531509

Odejide, O, Weigert, O, Lane, AA, Toscano, D, Lunning, MA, Kopp, N, Kim, S, Van Bodegom, D, Bolla, S, Schatz, JH, Teruya-Feldstein, J, Hochberg, E, Louissaint, A, Dorfman, D, Stevenson, K, Rodig, SJ, Piccaluga, PP, Jacobsen, E, Pileri, SA, Harris, NL, Ferrero, S, Inghirami, G, Horwitz, SM & Weinstock, DM 2014, 'A targeted mutational landscape of angioimmunoblastic T-cell lymphoma', Blood, vol. 123, no. 9, pp. 1293-1296. https://doi.org/10.1182/blood-2013-10-531509

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title = "A targeted mutational landscape of angioimmunoblastic T-cell lymphoma",

abstract = "The genetics of angioimmunoblastic T-cell lymphoma (AITL) are very poorly understood. We defined the mutational landscape of AITL across 219 genes in 85 cases from the United States and Europe. We identified ≥2 mutations in 34 genes, nearly all of which were not previously implicated in AITL. These included loss-of-function mutations in TP53 (n = 4), ETV6 (n = 3), CCND3 (n = 2), and EP300 (n = 5), as well as gain-of-function mutations in JAK2 (n = 2) and STAT3 (n = 4). TET2 was mutated in 65 (76\%) AITLs, including 43 that harbored 2 or 3 TET2 mutations. DNMT3A mutations occurred in 28 (33\%) AITLs; 100\% of these also harbored TET2 mutations (P < .0001). Seventeen AITLs harbored IDH2 R172 substitutions, including 15 with TET2 mutations. In summary, AITL is characterized by high frequencies of overlapping mutations in epigenetic modifiers and targetable mutations in a subset of cases.",

author = "Oreofe Odejide and Oliver Weigert and Lane, \{Andrew A.\} and Dan Toscano and Lunning, \{Matthew A.\} and Nadja Kopp and Sunhee Kim and \{Van Bodegom\}, Diederik and Sudha Bolla and Schatz, \{Jonathan H.\} and Julie Teruya-Feldstein and Ephraim Hochberg and Abner Louissaint and David Dorfman and Kristen Stevenson and Rodig, \{Scott J.\} and Piccaluga, \{Pier Paolo\} and Eric Jacobsen and Pileri, \{Stefano A.\} and Harris, \{Nancy L.\} and Simone Ferrero and Giorgio Inghirami and Horwitz, \{Steven M.\} and Weinstock, \{David M.\}",

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doi = "10.1182/blood-2013-10-531509",

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AU - Odejide, Oreofe

AU - Weigert, Oliver

AU - Lane, Andrew A.

AU - Toscano, Dan

AU - Lunning, Matthew A.

AU - Kopp, Nadja

AU - Kim, Sunhee

AU - Van Bodegom, Diederik

AU - Bolla, Sudha

AU - Schatz, Jonathan H.

AU - Teruya-Feldstein, Julie

AU - Hochberg, Ephraim

AU - Louissaint, Abner

AU - Dorfman, David

AU - Stevenson, Kristen

AU - Rodig, Scott J.

AU - Piccaluga, Pier Paolo

AU - Jacobsen, Eric

AU - Pileri, Stefano A.

AU - Harris, Nancy L.

AU - Ferrero, Simone

AU - Inghirami, Giorgio

AU - Horwitz, Steven M.

AU - Weinstock, David M.

PY - 2014/2/27

Y1 - 2014/2/27

N2 - The genetics of angioimmunoblastic T-cell lymphoma (AITL) are very poorly understood. We defined the mutational landscape of AITL across 219 genes in 85 cases from the United States and Europe. We identified ≥2 mutations in 34 genes, nearly all of which were not previously implicated in AITL. These included loss-of-function mutations in TP53 (n = 4), ETV6 (n = 3), CCND3 (n = 2), and EP300 (n = 5), as well as gain-of-function mutations in JAK2 (n = 2) and STAT3 (n = 4). TET2 was mutated in 65 (76%) AITLs, including 43 that harbored 2 or 3 TET2 mutations. DNMT3A mutations occurred in 28 (33%) AITLs; 100% of these also harbored TET2 mutations (P < .0001). Seventeen AITLs harbored IDH2 R172 substitutions, including 15 with TET2 mutations. In summary, AITL is characterized by high frequencies of overlapping mutations in epigenetic modifiers and targetable mutations in a subset of cases.

AB - The genetics of angioimmunoblastic T-cell lymphoma (AITL) are very poorly understood. We defined the mutational landscape of AITL across 219 genes in 85 cases from the United States and Europe. We identified ≥2 mutations in 34 genes, nearly all of which were not previously implicated in AITL. These included loss-of-function mutations in TP53 (n = 4), ETV6 (n = 3), CCND3 (n = 2), and EP300 (n = 5), as well as gain-of-function mutations in JAK2 (n = 2) and STAT3 (n = 4). TET2 was mutated in 65 (76%) AITLs, including 43 that harbored 2 or 3 TET2 mutations. DNMT3A mutations occurred in 28 (33%) AITLs; 100% of these also harbored TET2 mutations (P < .0001). Seventeen AITLs harbored IDH2 R172 substitutions, including 15 with TET2 mutations. In summary, AITL is characterized by high frequencies of overlapping mutations in epigenetic modifiers and targetable mutations in a subset of cases.

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JO - Blood

JF - Blood

IS - 9

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A targeted mutational landscape of angioimmunoblastic T-cell lymphoma

Abstract

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