间变性淋巴瘤激酶阳性和阴性间变性大细胞淋巴瘤分子遗传学研究

目的：研究间变性大细胞淋巴瘤（ALCL）的遗传学特征，探讨其发病机制，寻找有助于ALCL诊断、分类及预后评估的新分子靶标。方法收集ALCL病例石蜡包埋组织10例，其中4例间变性淋巴瘤激酶（ALK）阳性，6例ALK阴性。采用免疫组织化学染色及荧光原位杂交技术分别检测表型及2p23重排，利用OncoScan芯片在全基因组水平上扫描分析10例ALCL的拷贝数变异。结果10例ALCL均存在拷贝数变异，拷贝数获得者多于拷贝数缺失者。拷贝数获得主要累及17q11.2、Xp22.3、Xq28，拷贝数缺失主要累及3q26.1、14q11.2、22q11.23。 ALK阴性者拷贝数变异比ALK阳性者更为复杂：ALK阴性者拷贝数获得主要累及9q24.3-24.1、14q32.33，拷贝数缺失主要累及2p11.2、16p13.3，而ALK阳性者并无此变异。结论 ALCL存在复杂的遗传学不平衡，染色体片段获得多于缺失，ALK阴性ALCL遗传学不平衡更为复杂。 ALCL是异质性明显的一类肿瘤。

Molecular genetics of ALK-positive and ALK-negative anaplastic large-cell lymphoma

Objective To explore the genetic features of anaplastic large-cell lymphoma (ALCL) and its pathogenesis, and to detect the molecular targets for the diagnosis, classification and prognosis evaluation of ALCL. Methods Ten cases of ALCL were collected, respectively including 4 anaplastic lymphoma kinase (ALK)-positive and 6 ALK-negative. The immunophenotype and 2p23 rearrangement were detected by using IHC and fluorescence in situ hybridization, and OncoScan chip was applied to scan the copy number variation. Results Chromosomal imbalances were detected in all ALCL. The gain of copy number was more than the loss of copy number, The gain of copy number was mainly involved in 17q11.2, Xp22.3 and Xq28; the loss of copy number was mainly involved in 3q26.1, 14q11.2 and 22q11.23. The number variation in ALK-negative ALCL was more complicated than ALK-positive ALCL, the gain of copy number was mainly involved in 9q24.3-24.1 and 14q32.33, the loss of copy number was mainly involved in 2p11.2 and 16p13.3, but ALK-positive cases had no such variation. Conclusions ALK-positive and ALK-negative ALCL have different secondary genomic aberrations. Chromosomal imbalances are more complicated in ALK-negative ALCL that is featured by obvious heterogeneity.