Follicular lymphoma and classic Hodgkin lymphoma can be associated in composite and/or sequential lymphomas. Common IGH and BCL2 rearrangements have already been identified between both contingents of these entities, but mutation profiles have not yet been investigated. The main objective of this study was to analyze the transdifferentiation process that may occur between Hodgkin and follicular contingents in sequential and composite lymphomas to better characterize these entities. From 2004 to 2020, a retrospective multicentric study was performed, including 9 composite and 13 sequential lymphomas. Clinical data were retrospectively collected. Fluorescent in situ hybridization of BCL2 and BCL6 rearrangements, polymerase chain reaction of IGH and IGK rearrangements, next-generation sequencing of IGK rearrangement, and targeted next-generation sequencing (TNGS) on a panel of genes frequently mutated in lymphomas were performed on each contingent of composite and sequential lymphomas. For TNGS, each contingent was isolated by laser capture microdissection. Clinical presentation and evolution were more aggressive in sequential than composite lymphomas. By fluorescent in situ hybridization, common rearrangements of BCL6 and BCL2 were identified between both contingents. Similarly, a common clonal relationship was established by evaluating IGH and IGK rearrangement by polymerase chain reaction or next-generation sequencing. By TNGS, the same pathogenic variants were identified in both contingents in the following genes: CREBBP, KMT2D, BCL2, EP300, SF3B1, SOCS1, ARID1A, and BCOR. Specific pathogenic variants for each contingent were also identified: XPO1 for Hodgkin lymphoma contingent and FOXO1, TNFRSF14 for follicular lymphoma contingent. This study reinforces the hypothesis of a transdifferentiation process between Hodgkin and follicular contingent of sequential/composite lymphomas.

中文翻译：

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滤泡性和经典霍奇金淋巴瘤之间成熟 B 细胞的可塑性：一系列 22 例扩大转分化谱的病例。

滤泡性淋巴瘤和经典霍奇金淋巴瘤可能与复合性和/或序贯性淋巴瘤有关。已经在这些实体的两个特遣队之间确定了常见的 IGH 和 BCL2 重排，但尚未研究突变谱。本研究的主要目的是分析顺序和复合淋巴瘤中霍奇金和滤泡特遣队之间可能发生的转分化过程，以更好地表征这些实体。从 2004 年到 2020 年，进行了一项回顾性多中心研究，包括 9 例复合淋巴瘤和 13 例连续淋巴瘤。回顾性收集临床数据。BCL2和BCL6重排的荧光原位杂交，IGH和IGK重排的聚合酶链反应，IGK重排的下一代测序，对一组在淋巴瘤中经常发生突变的基因进行靶向二代测序（TNGS），对复合和连续淋巴瘤的每个特遣队进行。对于 TNGS，通过激光捕获显微切割分离每个特遣队。序贯淋巴瘤的临床表现和演变比复合淋巴瘤更具侵袭性。通过荧光原位杂交，在两个特遣队之间鉴定了 BCL6 和 BCL2 的常见重排。同样，通过聚合酶链反应或二代测序评估 IGH 和 IGK 重排，建立了共同的克隆关系。通过 TNGS，在两个特遣队的以下基因中鉴定出相同的致病变异：CREBBP、KMT2D、BCL2、EP300、SF3B1、SOCS1、ARID1A 和 BCOR。还确定了每个特遣队的特定致病变异：XPO1 用于霍奇金淋巴瘤特遣队，FOXO1、TNFRSF14 用于滤泡性淋巴瘤特遣队。这项研究强化了霍奇金和连续/复合淋巴瘤的滤泡特遣队之间的转分化过程的假设。