Rarity of microsatellite genomic instability in B‐cell non‐Hodgkin's lymphomas in hepatitis C virus‐infected patients

Abstract

Summary. Several groups have emphasized the likely implication of the hepatitis C virus (HCV) in a fraction of B-cell nonHodgkin's lymphomas. Since only a minority of patients with HCV infection and monoclonal mixed cryoglobulinaemia develop overt lymphoma, the identification of predisposing factors has relevant clinical implications. The replication error phenotype (RER þ ), as revealed by widespread microsatellite instability, is caused by defects in DNA mismatch repair genes, and has been frequently disclosed in subsets of B-cell lymphomas with underlying infection and chronic inflammation. We therefore investigated the occurrence of the RER þ phenotype in a series of eight consecutive B-cell NHLs in patients with chronic infec-tion by HCV. A polymerase chain reaction-based assay was used to analyse an extended panel of 15 microsatellite loci.Microsatellite instability was not observed in six tumour samples in any locus; the two remaining cases showed instability at only one locus.Therefore genetic instability by defects in DNA mismatch repair genes should not represent the general mechanism predisposing to overt lymphoma in HCV-infected patients. Although a clearer definition of HCV-related B-cell disorders should better address future studies on genetic instability in larger series, we recommend additional oncogenetic pathways as the target of further research.

Oligoclonal non-neoplastic B cell expansion is the key feature of type II mixed cryoglobulinemia: Clinical and molecular findings do not support a bone marrow pathologic diagnosis of indolent B cell lymphoma

“…The results of molecular studies fully support the concept of a true B cell malignancy when a clinically overt lymphoma develops. Further efforts are needed to identify the MC patients who will develop such overt malignancy (10,41), and diagnosis of bone marrow indolent lymphoma solely on pathologic grounds appears insufficient to this end. The integration of molecular analyses of B cell clonality with clinical and pathologic findings may be crucial to better elucidate this issue.…”

Analysis of the frequency of microsatellite instability and p53 gene mutation in splenic marginal zone and MALT lymphomas

“…50 In contrast with this finding, research into hepatitis C virus associated lymphoma has not shown microsatellite instability to be present. 48 The role of microsatellite instability in neoplastic transformation has been the subject of recent investigations. Microsatellite instability has been implicated as a pathogenetic mechanism in subsets of tumours linked pathogenically to chronic infection and inflammation, such as tumours occurring after schistosomiasis, viral hepatitis B, chronic ulcerative colitis, or papillomavirus infection.…”

Mismatch repair deficiency in hematological malignancies with microsatellite instability

“…Hematological malignancies have been reported to display microsatellite instability (De Vita et al, 1997;Hayami et al, 1999;Kaneko et al, 1996;Kodera et al, 1999;Larson et al, 1997), but whether they are also deficient in MMR was still a matter of debate. To help resolve this issue, we studied MMR proficiency in several hematological cancer cell lines, using both biochemical and genetic analyses, and our results suggest that a significant portion of hematological cancer cells with MSI are MMR defective.…”

“…In addition to its demonstration in solid tumors, MSI has also been observed in hematological malignancies (De Vita et al, 1997;Hayami et al, 1999;Kaneko et al, 1996;Kodera et al, 1999;Larson et al, 1997). However, whether these hematological malignancies are associated with MMR defects is still controversial.…”