ALK阳性大B细胞淋巴瘤：七例临床病理和分子特征分析
ALK-positive large B-cell lymphoma: a clinicopathological and molecular characteristics analysis of seven cases
影响因子:3.00000
分区:医学3区 / 病理学3区
发表日期:2024 Dec
作者:
Xuan Wang, Hongmei Yi, Qingxiao Liu, Tuanjie Guo, Anqi Li, Binshen Ouyang, Yimin Li, Yuxiu Zhang, Haimin Xu, Lei Dong, Xu Wang, Chaofu Wang
摘要
变性淋巴瘤激酶阳性大B细胞淋巴瘤（ALK+ LBCL）是一种罕见且高度攻击性的淋巴瘤，具有特征性的ALK重排。已经证明了涉及ALK的各种融合基因，但是ALK融合伙伴对ALK蛋白表达和ALK+ LBCL的遗传特征的影响仍然相对未知。在这项研究中，我们对七个ALK+ LBCL病例进行了广泛的临床病理和分子分析，以探索ALK融合基因与ALK蛋白表达之间的相关性，从而丰富了该肿瘤的遗传特征。我们整合了临床，组织病理学/免疫表型和分子研究的发现，包括三个接受下一代测序的样本，六例接受了基于RNA的ALK融合基因检测。我们确定了五种不同类型的ALK融合基因，包括CLTC，NPM1，PABPC1，SEC31A和TFG。值得注意的是，只有NPM1 :: ALK融合显示核和细胞质ALK染色，其余四个融合基因导致细胞质ALK染色。我们的分析表明，CLTC :: ALK融合产生了独特的细胞质核周核高尔基区局灶性颗粒状颗粒状异质染色模式。此外，我们确定了六个潜在具有临床意义的基因突变，包括TET2，CHD2，DTX1，KMT2D，LRP1B和XPO1。此外，在所有情况下，都观察到没有5-羟基甲基胞嘧啶（5HMC）。我们介绍了七个ALK+ LBCL病例，讨论了融合基因与ALK蛋白表达之间的相关性，并增强了我们对该肿瘤遗传属性的理解。这项研究还显示了几乎所有七个ALK+ LBCL病例中5HMC的损失，与TET2突变无关。
Abstract
Anaplastic lymphoma kinase-positive large B-cell lymphoma (ALK+ LBCL) is a rare and highly aggressive lymphoma with characteristic ALK rearrangements. Various fusion genes involving ALK have been demonstrated, but the influence of the ALK fusion partners on ALK protein expression and the genetic characteristics of ALK+ LBCL remain relatively unknown. In this study, we conducted an extensive clinicopathological and molecular analysis on seven cases of ALK+ LBCL to explore the correlation between ALK fusion genes and ALK protein expression, thereby enriching the genetic characteristics of this tumour. We integrated the findings from clinical, histopathological/immunophenotypic, and molecular studies, including three samples subjected to next-generation sequencing, and six cases underwent RNA-based ALK fusion gene detection. We identified five distinct types of ALK fusion genes, including CLTC, NPM1, PABPC1, SEC31A, and TFG. Notably, only the NPM1::ALK fusion showed nuclear and cytoplasmic ALK staining, and the remaining four fusion genes resulted in cytoplasmic ALK staining. Our analysis revealed that the CLTC::ALK fusion resulted in a unique cytoplasmic perinuclear Golgi zone focal granular heterogeneous staining pattern of ALK. Additionally, we identified six potentially clinically significant gene mutations, including TET2, CHD2, DTX1, KMT2D, LRP1B, and XPO1. Furthermore, in all cases, the absence of 5-hydroxymethylcytosine (5hmC) was observed. We present seven cases of ALK+ LBCL, discussing the correlation between fusion genes and ALK protein expression, and enhancing our understanding of the genetic attributes of this tumour. This study also shows the loss of 5hmC in nearly all seven ALK+ LBCL cases, independently of TET2 mutations.