A targeted mutational landscape of angioimmunoblastic T-cell lymphoma
A targeted mutational landscape of angioimmunoblastic T-cell lymphoma
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DOI：
10.1182/blood-2013-10-531509
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发表时间：
2014-02-27
期刊：
影响因子：
20.3
通讯作者：
Weinstock, David M.
中科院分区：
文献类型：
--
作者：
Odejide, Oreofe;Weigert, Oliver;Weinstock, David M.
血管免疫母细胞性T细胞淋巴瘤（AITL）的遗传学知之甚少。我们定义了来自美国和欧洲的85例病例中219个基因的AITL突变景观。我们在34个基因中发现了>= 2个突变，几乎所有这些突变都与AITL无关。这些包括TP 53（n = 4）、ETV 6（n = 3）、CCND 3（n = 2）和EP 300（n = 5）中的功能丧失突变，以及JAK 2（n = 2）和STAT 3（n = 4）中的功能获得突变。TET 2在65例（76%）AITL中发生突变，包括43例携带2或3个TET 2突变。DNMT 3A突变发生在28例（33%）AITL中;其中100%还携带TET 2突变（P < .0001）。17个AITL具有IDH 2 R172取代，包括15个TET 2突变。总之，AITL的特征在于表观遗传修饰因子中的重叠突变和病例子集中的靶向突变的高频率。
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.