Two recurrent types of IGH::5' BCL2 breakpoints representing cytogenetic ins(14;18)(q32;q21q21) and t(14;18)(q32;q21), mediated by the VDJ and class switch recombination processes, respectively

Fumiyo Maekawa; Masahiko Hayashida; Kayo Takeoka; Katsuhiro Fukutsuka; Miho Nakagawa; Takashi Akasaka; Shinichi Sakamoto; Shinji Sumiyoshi; Yoichiro Kobashi; Hitoshi Ohno

doi:10.1080/10428194.2024.2341333

Two recurrent types of IGH::5' BCL2 breakpoints representing cytogenetic ins(14;18)(q32;q21q21) and t(14;18)(q32;q21), mediated by the VDJ and class switch recombination processes, respectively

Leuk Lymphoma. 2024 Apr 12:1-10. doi: 10.1080/10428194.2024.2341333. Online ahead of print.

Affiliations

¹ Tenri Institute of Medical Research, Tenri Hospital, Tenri, Nara, Japan.
² Department of Hematology, Tenri Hospital, Tenri, Nara, Japan.
³ Department of Diagnostic Pathology, Tenri Hospital, Tenri, Nara, Japan.

PMID: 38608254
DOI: 10.1080/10428194.2024.2341333

Abstract

We describe two types of IGH::BCL2 breakpoints involving the 5' region of BCL2 (5' BCL2). One was ins(14;18)(q32;q21q21) observed in 2 follicular lymphoma (FL) cases, in which IGH was cleaved at 3' of IGHD and 5' of IGHJ and BCL2 was cleaved at 5' BCL2 and downstream regions, and a 281- or 201-kilobase pair fragment containing the BCL2 protein-coding sequences was invertedly inserted into IGH. In another type observed in 2 FL and 2 chronic lymphocytic leukemia (CLL) cases, breakage and reunion occurred within the switch region associated with IGHM (Sµ) and 5' BCL2, creating IGH Sµ::5' BCL2 fusion sequences on der(18)t(14;18)(q32;q21). The former is considered to be mediated by VDJ-recombination, while the latter by the class switch recombination process. There were no particular features in FL or CLL cases with IGH::5' BCL2 breakpoints compared with those with t(14;18)(q32;q21)/IGH::BCL2 involving the 3' breakpoint cluster regions.

Keywords: Follicular lymphoma; chronic lymphocytic leukemia; class switch recombination; ins(14;18)(q32;q21q21;), IGH::5′ BCL2 breakpoints; next generation sequencing.