TY - JOUR
T1 - A targeted mutational landscape of angioimmunoblastic T-cell lymphoma
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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U2 - 10.1182/blood-2013-10-531509
DO - 10.1182/blood-2013-10-531509
M3 - Article
C2 - 24345752
AN - SCOPUS:84896617557
VL - 123
SP - 1293
EP - 1296
JO - Blood
JF - Blood
SN - 0006-4971
IS - 9
ER -