Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA;
Blood. 2014 Feb 27;123(9):1293-6. doi: 10.1182/blood-2013-10-531509. Epub 2013 Dec 17.
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.
血管免疫母细胞性 T 细胞淋巴瘤（AITL）的遗传学机制还知之甚少。我们在 85 例来自美国和欧洲的病例中检测了 219 个基因的突变情况，定义了 AITL 的突变图谱。我们在 34 个基因中发现了≥2 个突变，几乎所有突变之前都没有与 AITL 相关。这些突变包括 TP53（n=4）、ETV6（n=3）、CCND3（n=2）和 EP300（n=5）的功能丧失性突变，以及 JAK2（n=2）和 STAT3（n=4）的功能获得性突变。TET2 突变发生在 65 例（76%）AITL 中，其中 43 例存在 2 或 3 个 TET2 突变。DNMT3A 突变发生在 28 例（33%）AITL 中；这些病例 100%都存在 TET2 突变（P<0.0001）。17 例 AITL 存在 IDH2 R172 取代，其中 15 例存在 TET2 突变。总之，AITL 的特点是表观遗传修饰物的重叠突变频率较高，部分病例存在可靶向突变。
