Optical Genome Mapping Reveals Diverse Mechanisms of Cyclin Activation in Mantle Cell Lymphomas Lacking IGH::CCND1.

Journal: Human Pathology
Published:
Abstract

The t(11;14)(q13;q32)/IGH::CCND1 is a genetic hallmark of mantle cell lymphoma (MCL), reported to be present in about 95% of cases. In this study, we performed optical genome mapping (OGM) on 91 patients with MCL, in conjunction with next-generation sequencing (NGS), conventional chromosomal analysis and fluorescence in situ hybridization (FISH). The t(11;14)/IGH::CCND1 was detected in 82 cases, whereas 9 (10%) cases lacked this abnormality. OGM and NGS identified alternative CCND1 abnormalities in 7 cases: IGK::CCND1 (n=3), IGL::CCND1 (n=1), an insertion adjacent to the 5' region of CCND1 (n=1); a deletion at the 5' region of CCND1 (n=1), and a mutation in the 3' untranslated region of CCND1 (n=1). OGM detected CCND2 rearrangement with IGK or IGL in the other 2 cases. All 7 cases exhibiting CCND1 aberrations expressed cyclin D1, although some lacked SOX11 or CD5 expression. The two cases with CCND2 rearrangement were SOX11-positive. Six cases showed highly complex genome detected by OGM and the affected patients were refractory to chemotherapy and/or had poorer survival. In conclusion, approximately 10% of MCL cases lack the classic t(11;14)/IGH::CCND1. OGM is valuable in identifying variant CCND1 and CCND2 rearrangements, and the presence of high genome complexity may correlate with treatment resistance and poor outcomes.

Authors
Guilin Tang, Preetesh Jain, Shimin Hu, Chi Ok, Wei Wang, Andres Quesada, Qing Wei, Shaoying Li, Jie Xu, Sanam Loghavi, Gocke Toruner, L Medeiros