B-Lymphoblastic Lymphomas Evolving from Follicular Lymphomas Co-Express Surrogate Light Chains and Mutated Gamma Heavy Chains

Linda M. Slot, Robbert Hoogeboom, Laura A. Smit, Thera A. M. Wormhoudt, Bart J. Biemond, Monique E. C. M. Oud, Esther J. M. Schilder-Tol, Andre B. Mulder, Aldo Jongejan, Antoine H. C. van Kampen, Philippus Kluin, Jeroen E. J. Guikema, Richard J. Bende, Carel J. M. van Noesel*

*Bijbehorende auteur voor dit werk

OnderzoeksoutputAcademicpeer review

17 Citaten (Scopus)

Samenvatting

Follicular Lymphoma (FL) is an indolent B-cell non-Hodgkin lymphoma able to transform into germinal center-type diffuse large B-cell lymphoma. We describe four extraordinary cases of FL, which progressed to TdT(+)CD20(-) precursor B-lymphoblastic lymphoma (B-LBL). Fluorescence in situ hybridization analysis showed that all four B-LBLs had acquired a MYC translocation on transformation. Comparative genomic hybridization analysis of one case demonstrated that in addition to 26 numerical aberrations that were shared between the FL and B-LBL, deletion of CDKN2A/B and 17q11, 14q32 amplification, and copy neutral loss of heterozygosity of 9p were gained in the B-LBL cells. Whole-exome sequencing revealed mutations in FMN2, NEB, and SYNE1 and a nonsense mutation in KMT2D, all shared by the FL and B-LBL, and TNFRSF14, SMARCA2, CCND3 mutations uniquely present in the B-LBL. Remarkably, all four FL B-LBL pairs expressed IgG. In two B-LBLs, evidence was obtained for ongoing rearrangement of 16 light chain variable genes and expression of the surrogate light chain. IGHV mutation analysis showed that all FL B-LBL pairs harbored identical or near-identical somatic mutations. From the somatic gene alterations found in the IG and non-IG genes, we conclude that the FLs and B-LBLs did not develop in parallel from early t(14;18)-positive IG-unmutated precursors, but that the B-LBLs developed from preexistent FL subclones that accumulated additional genetic damage.

Originele taal-2English
Pagina's (van-tot)3273-3284
Aantal pagina's12
TijdschriftThe American Journal of Pathology
Volume186
Nummer van het tijdschrift12
DOI's
StatusPublished - dec-2016

Citeer dit