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

Istituto Europeo di Oncologia

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

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
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
Publication status	Published - Feb 27 2014

ASJC Scopus subject areas

Hematology
Biochemistry
Cell Biology
Immunology

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10.1182/blood-2013-10-531509

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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

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

In: Blood, Vol. 123, No. 9, 27.02.2014, p. 1293-1296.

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

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

Odejide, Oreofe ; Weigert, Oliver ; Lane, Andrew A. ; Toscano, Dan ; Lunning, Matthew A. ; Kopp, Nadja ; Kim, Sunhee ; Van Bodegom, Diederik ; Bolla, Sudha ; Schatz, Jonathan H. ; Teruya-Feldstein, Julie ; Hochberg, Ephraim ; Louissaint, Abner ; Dorfman, David ; Stevenson, Kristen ; Rodig, Scott J. ; Piccaluga, Pier Paolo ; Jacobsen, Eric ; Pileri, Stefano A. ; Harris, Nancy L. ; Ferrero, Simone ; Inghirami, Giorgio ; Horwitz, Steven M. ; Weinstock, David M. / A targeted mutational landscape of angioimmunoblastic T-cell lymphoma. In: Blood. 2014 ; Vol. 123, No. 9. pp. 1293-1296.

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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.",

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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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A targeted mutational landscape of angioimmunoblastic T-cell lymphoma

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