Detection of cryptic CCND1 rearrangements in mantle cell lymphoma by next generation sequencing


Polonis K, et al. Ann Diagn Pathol 2020.


The accurate detection of recurrent genetic abnormalities for most hematologic neoplasms is critical for diagnosis, prognosis and/or treatment. Rearrangements involving CCND1 are observed in a subset of mature B-cell neoplasms and can be reliably detected by fluorescence in situ hybridization (FISH) in most cases. However, cryptic and complex chromosomal rearrangements may pose a technical challenge for accurate diagnosis. Herein, we describe two patients with suspected mantle cell lymphoma that

lacked obvious CCND1 rearrangements by FISH studies. A next generation sequencing (NGS) based assay, mate-pair sequencing (MPseq), was utilized in each case to investigate potential cryptic CCND1 rearrangements and revealed cryptic insertional events resulting in CCND1/IGH and CCND1/IGK rearrangements. These cases demonstrate that NGS-based assays, including MPseq, are a powerful approach to identify cryptic rearrangements of clinical importance that are not detected by current clinical genomics evaluation.