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

Research output: Contribution to journalArticle

149 Citations (Scopus)

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 languageEnglish (US)
Pages (from-to)1293-1296
Number of pages4
JournalBlood
Volume123
Issue number9
DOIs
StatePublished - Feb 27 2014
Externally publishedYes

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T-cells
T-Cell Lymphoma
Mutation
Genes
Substitution reactions
Mutation Rate
Epigenomics

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Odejide, O., Weigert, O., Lane, A. A., Toscano, D., Lunning, M. A., Kopp, N., ... 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 journalArticle

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 O, Weigert O, Lane AA, Toscano D, Lunning MA, Kopp N et al. A targeted mutational landscape of angioimmunoblastic T-cell lymphoma. Blood. 2014 Feb 27;123(9):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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AU - Kopp, Nadja

AU - Kim, Sunhee

AU - Van Bodegom, Diederik

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AU - Piccaluga, Pier Paolo

AU - Jacobsen, Eric

AU - Pileri, Stefano A.

AU - Harris, Nancy L.

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AU - Inghirami, Giorgio

AU - Horwitz, Steven M.

AU - Weinstock, David M.

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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.

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