A targeted mutational landscape of angioimmunoblastic T-cell lymphoma

作者：Oreofe O. Odejide, Oliver Weigert, Andrew A. Lane, Daniel Toscano, Matthew A. Lunning, Nadja Kopp, Sunhee S. Kim, Diederik van Bodegom, Sudha Bolla, Jonathan H. Schatz, Julie Teruya‐Feldstein, Ephraim P. Hochberg, Abner Louissaint, David M. Dorfman, Kristen E. Stevenson, Scott J. Rodig, Pier Paolo Piccaluga, Eric D. Jacobsen, Stefano Pileri, Nancy L. Harris, Simone Ferrero, Giorgio Inghirami, Steven M. Horwitz, David M. Weinstock · 发表于：Blood · 年份：2013 · DOI：10.1182/blood-2013-10-531509 · 被引用次数：433 · 研究领域：Lymphoma Diagnosis and Treatment、Chronic Lymphocytic Leukemia Research、Acute Myeloid Leukemia Research

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.