title: Hypermutation in mantle cell lymphoma does not indicate a clinical or biological subentity.
abstract: Mantle cell lymphoma is a prime example of a well-defined entity based on morphology, phenotype, genetics and also clinical features. Although most patients have an adverse clinical course, some have a better survival than others. The most consistently reported adverse prognostic parameter is a high mitotic rate. Recently, it has been shown that hypermutation in the immunoglobulin heavy-chain gene occurs in a subset of mantle cell lymphomas. It is, however, unclear whether the mutational status is stable over time within a given case, whether hypermutation might be influenced by therapy and how it is related to other relevant biological features of mantle cell lymphoma. In this study, we analyzed 23 typical mantle cell lymphoma cases with respect to mutational status and compared the results with clinicopathological and genetic data to determine whether the presence of mutation indicates a subentity with clinical or pathological relevance. We found somatic hypermutation in 26% of our cases and, interestingly, one case showed ongoing somatic hypermutation. In tumor cells of both mutated and unmutated cases, we found a preferential usage of V(H)3-21 (23%) and V(H)4-34 (19%). No significant correlations were found between mutation status and the other morphological and genetic features analyzed. In conclusion, our results provide additional evidence that mutation status in mantle cell lymphoma is better interpreted as a feature within the spectrum of disease that seems to have little clinical or pathological relevance.
authors.affiliation: Department of Pathology, Radboud University Nijmegen Medical Centre, Nijmegen, the Netherlands.
authors.forename: Margit
authors.initials: M
authors.lastname: Schraders
authors.forename: Sabine
authors.initials: S
authors.lastname: Oeschger
authors.forename: Philip M
authors.initials: PM
authors.lastname: Kluin
authors.forename: Konnie
authors.initials: K
authors.lastname: Hebeda
authors.forename: Ed
authors.initials: E
authors.lastname: Schuuring
authors.forename: Patricia J T A
authors.initials: PJ
authors.lastname: Groenen
authors.forename: Martin-Leo
authors.initials: ML
authors.lastname: Hansmann
authors.forename: Johan H J M
authors.initials: JH
authors.lastname: van Krieken
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D015139:Blotting, Southern; D055028:Comparative Genomic Hybridization; D005260:Female; D006801:Humans; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D007146:Immunoglobulin lambda-Chains / Q000235:genetics; D007150:Immunohistochemistry; D020522:Lymphoma, Mantle-Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016133:Polymerase Chain Reaction; D027041:Somatic Hypermutation, Immunoglobulin / Q000235:genetics*
chemical_list: D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains