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

Polonis, Katarzyna; Schultz, Matthew J; Olteanu, Horatiu; Smadbeck, James B; Johnson, Sarah H; Vasmatzis, George; Xu, Xinjie; Greipp, Patricia T; Ketterling, Rhett P; Hoppman, Nicole L; Baughn, Linda B; Peterson, Jess F

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.