Tomita Sakura, Kikuti Yara Yukie, Carreras Joaquim, Sakai Rika, Takata Katsuyoshi, Yoshino Tadashi, Bea Silvia, Campo Elias, Missiaglia Edoardo, Bouilly Justine, Letourneau Audrey, de Leval Laurence, Nakamura Naoya
Department of Pathology, School of Medicine, Tokai University, 143 Shimokasuya, Kanagawa, Isehara 259-1193, Japan.
Department of Oncology, Kanagawa Cancer Center, Kanagawa, Yokohama 241-8515, Japan.
Cancers (Basel). 2020 Nov 27;12(12):3539. doi: 10.3390/cancers12123539.
Monomorphic epitheliotropic intestinal T-cell lymphoma (MEITL) is a rare primary T-cell lymphoma of the digestive tract derived from intraepithelial lymphocytes and characterized by an aggressive clinical course. In this study, nine cases of Japanese MEITL were analyzed by targeted Next Generation Sequencing (NGS) and immunohistochemistry and were integrated with previously reported whole-genome copy number microarray-based assay data. The highlight of our findings is that all cases showed alterations of the tumor suppressor gene by mutations and/or loss of the corresponding 3p21 locus. We also demonstrated that all cases showed mutations in one or more genes of JAK/STAT pathway. Therefore, the combination of epigenetic deregulation and cell signaling activation represent major oncogenic events in the pathogenesis of MEITL in Asian MEITL, similar to Western MEITL.
单形性上皮趋化性肠道T细胞淋巴瘤（MEITL）是一种罕见的原发性消化道T细胞淋巴瘤，起源于上皮内淋巴细胞，临床病程侵袭性强。在本研究中，对9例日本MEITL病例进行了靶向二代测序（NGS）和免疫组化分析，并与先前报道的基于全基因组拷贝数微阵列分析的数据相结合。我们研究结果的亮点是，所有病例均通过相应3p21位点的突变和/或缺失显示肿瘤抑制基因改变。我们还证明，所有病例均在JAK/STAT通路的一个或多个基因中发生突变。因此，与西方MEITL相似，表观遗传失调和细胞信号激活的组合代表了亚洲MEITL发病机制中的主要致癌事件。
