For the auxiliary diagnosis of mantle cell lymphoma (MCL) that is cyclin D1 expression negative or CCND1 deletion negative.

MCL is a subtype of aggressive B-cell non-Hodgkin lymphoma characterized by a distinctive CCND1-IGH translocation, leading to overexpression of cyclin D1 protein. However, gene expression profiling has identified a small subset of MCL cases that do not express cyclin D1 protein or exhibit CCND1-IGH translocation, yet these patients may show positive expression of cycD2 or cycD3. Among these, patients with cycD2 expression exhibit CCND2 locus gene translocations, with partner genes being IGH or IGK. CycD2 expression is not limited to MCL and can also be observed in various B-cell non-Hodgkin lymphomas; FISH methods are more accurate. In a study of 40 MCL patients with negative cyclin D1 expression, it was found that up to 55% of patients (22 cases) had CCND2 translocations, with 18 cases having partner genes from the IG gene family (particularly light chain genes, with 10 cases involving IGK and 5 cases involving IGL). The authors concluded that CCND2 translocations are the most common genetic abnormality in MCL patients with negative cyclin D1 expression.

Additionally, it has been reported that cyclin D1-negative MCL patients with CCND2-IGL fusions exhibit blast-like morphology and aggressive clinical behavior upon relapse.