Mantle Cell Lymphoma FISH Probes

ATM deletion is one of the most frequent secondary alterations in MCL. ATM inactivation in naïve mantle zone cells is thought to promote genomic instability, as MCL patients with ATM mutations tend to have a higher number of chromosomal abnormalities.

CCND1/IGH fusion is present in virtually all cases of MCL. The fusion causes cyclin D1, which is not expressed in normal B lymphocytes, to be constitutively overexpressed. It’s likely the primary event in pathogenesis of MCL.

CDK4 amplification is found in 21% of highly proliferative MCL. The alteration is evidence of the importance of G1-S phase disruption in MCL pathogenesis, as CDK4 is a central cell cycle regulator.

Homozygous CDKN2A deletion occurs in 20–30% of the highly proliferative variants of MCL, but in less than 5% of the typical cases. CDKN2A inactivation leads to deregulation of the cell cycle and the p53 pathway.