To further unravel the molecular pathogenesis of diffuse large B-cell lymphoma (DLBCL), a high-resolution comparative genomic hybridization on lymph node biopsies from 70 patients was performed. With this strategy, microdeletions of genes involved in the mutation mismatch repair (MMR) pathway were identified in two samples. The first patient presented a homozygous deletion of MSH2-MSH6 due to duplication of an unbalanced pericentric inversion of chromosome 2. The other case showed a PMS2 heterozygous deletion. PMS2 and MSH2-MSH6 abnormalities, respectively, resulted in a decrease and complete loss of gene expression. However, unlike tumors associated with the hereditary non-polyposis colorectal cancer syndrome or immunodeficiency-related lymphomas, no microsatellite instability was detected. These findings suggest that in a rare subset of patients, inactivation of the genes of the MMR pathway is likely an important step in the molecular pathogenesis of DLBCL and does not involve the same molecular mechanisms as other common neoplasms with MMR deficiency.
