Department of Hematology, Aarhus University Hospital.
Department of Clinical Medicine, Aarhus University.
AIDS. 2024 Nov 15;38(14):1897-1906. doi: 10.1097/QAD.0000000000003996. Epub 2024 Aug 22.
Individuals with HIV experience an increased risk of lymphoma, making this an important cause of death among people with HIV. Nevertheless, little is known regarding the underlying genetic aberrations, which we therefore set out to characterize.
We conducted next-generation panel sequencing to explore the mutational status of diagnostic lymphoma biopsies from 18 patients diagnosed with lymphoma secondary to HIV infection.
Ion Torrent next-generation sequencing was performed with an AmpliSeq panel on diagnostic lymphoma biopsies from HIV-associated B-cell lymphomas ( n = 18), comprising diffuse large B-cell lymphoma ( n = 9), classic Hodgkin lymphoma ( n = 6), Burkitt lymphoma ( n = 2), follicular lymphoma ( n = 1), and marginal zone lymphoma ( n = 1). The panel comprised 69 lymphoid and/or myeloid-relevant genes, in which either the entire coding sequence or a hotspot region was sequenced.
Among the 18 lymphomas, we detected 213 variants. The number of detected mutations ranged from 4 to 41 per tumor distributed among 42 genes, including both exonic and intronic regions. The most frequently mutated genes included KMT2D (67%), TNFAIP3 (50%), and TP53 (61%). Notably, no gene was found to harbor variants across all the HIV-associated lymphomas, nor did we find subtype-specific variants. While some variants were shared among patients, most were unique to the individual patient and were often not reported as malignant genetic variants in databases.
Our findings demonstrate genetic heterogeneity across histological subtypes of HIV-associated lymphomas and thus help elucidate the genetics and pathophysiological mechanisms underlying the disease.
HIV 感染者罹患淋巴瘤的风险增加，这使其成为 HIV 感染者的重要死亡原因。然而，人们对潜在的遗传异常知之甚少，因此我们着手对其进行研究。
我们对 18 例 HIV 相关 B 细胞淋巴瘤继发淋巴瘤患者的诊断性淋巴瘤活检标本进行了下一代靶向测序，以探索其突变状态。
采用 Ion Torrent 下一代测序仪和 AmpliSeq panel 对 18 例 HIV 相关 B 细胞淋巴瘤（弥漫性大 B 细胞淋巴瘤 9 例，经典霍奇金淋巴瘤 6 例，伯基特淋巴瘤 2 例，滤泡性淋巴瘤 1 例，边缘区淋巴瘤 1 例）的诊断性淋巴瘤活检标本进行检测。该 panel 包含 69 个淋巴和/或髓系相关基因，其中包含整个编码序列或热点区域。
在这 18 例淋巴瘤中，我们检测到 213 种变异。每个肿瘤的检测突变数量从 4 到 41 个，分布在 42 个基因中，包括外显子和内含子区域。突变频率最高的基因包括 KMT2D（67%）、TNFAIP3（50%）和 TP53（61%）。值得注意的是，我们没有发现所有 HIV 相关淋巴瘤都存在变异的基因，也没有发现亚型特异性变异。虽然一些变异在患者之间共享，但大多数变异是个体患者所特有的，且这些变异在数据库中通常不被认为是恶性遗传变异。
我们的研究结果表明，HIV 相关淋巴瘤的组织学亚型存在遗传异质性，有助于阐明该疾病的遗传和病理生理学机制。
