Higher grade transformation of follicular lymphoma: phenotypic tumor progression associated with diverse genetic lesions.

Higher grade histological transformation of follicular lymphoma (FL) to more aggressive diffuse large B-cell lymphomas (DLBCL) occurs in 10-60% of the cases. Review of the current knowledge of genetic and molecular alterations associated with the higher grade transformation of FCL suggests that the process that leads to clinically and phenotypically similar end-point can occur by functionally diverse genetic lesions. The most commonly identified genetic alterations associated with the FCL transformation are TP53 gene mutations, inactivation of CDKN2A and CDKN2B genes and deregulation of the C-MYC gene. These lesions affect different aspects of normal cell physiology (apoptosis, cell cycle control, and proliferation) and are potential targets for gene-specific therapies.