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.
authors.affiliation: Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA;
authors.forename: Oreofe
authors.initials: O
authors.lastname: Odejide
authors.forename: Oliver
authors.initials: O
authors.lastname: Weigert
authors.forename: Andrew A
authors.initials: AA
authors.lastname: Lane
authors.forename: Dan
authors.initials: D
authors.lastname: Toscano
authors.forename: Matthew A
authors.initials: MA
authors.lastname: Lunning
authors.forename: Nadja
authors.initials: N
authors.lastname: Kopp
authors.forename: Sunhee
authors.initials: S
authors.lastname: Kim
authors.forename: Diederik
authors.initials: D
authors.lastname: van Bodegom
authors.forename: Sudha
authors.initials: S
authors.lastname: Bolla
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Schatz
authors.forename: Julie
authors.initials: J
authors.lastname: Teruya-Feldstein
authors.forename: Ephraim
authors.initials: E
authors.lastname: Hochberg
authors.forename: Abner
authors.initials: A
authors.lastname: Louissaint
authors.forename: David
authors.initials: D
authors.lastname: Dorfman
authors.forename: Kristen
authors.initials: K
authors.lastname: Stevenson
authors.forename: Scott J
authors.initials: SJ
authors.lastname: Rodig
authors.forename: Pier Paolo
authors.initials: PP
authors.lastname: Piccaluga
authors.forename: Eric
authors.initials: E
authors.lastname: Jacobsen
authors.forename: Stefano A
authors.initials: SA
authors.lastname: Pileri
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Harris
authors.forename: Simone
authors.initials: S
authors.lastname: Ferrero
authors.forename: Giorgio
authors.initials: G
authors.lastname: Inghirami
authors.forename: Steven M
authors.initials: SM
authors.lastname: Horwitz
authors.forename: David M
authors.initials: DM
authors.lastname: Weinstock
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D005260:Female; D005787:Gene Frequency; D006801:Humans; D007119:Immunoblastic Lymphadenopathy / Q000453:epidemiology / Q000235:genetics*; D016399:Lymphoma, T-Cell / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation