title: Blastic variant of mantle cell lymphoma shows a heterogenous pattern of somatic mutations of the rearranged immunoglobulin heavy chain variable genes.
abstract: Mantle cell lymphoma is a distinct clinicopathological entity associated with t(11;14) and cyclin D1 overexpression. The majority of cases show uniform morphological and phenotypic features characterized by a monotonous proliferation of small-to-medium-sized irregular B cells that express CD5 and bright surface immunoglobulin IgM and IgD. By sequence analysis of the rearranged immunoglobulin heavy chain variable genes (VH), it has been shown that these lymphoma cells carry little if no somatic mutations, as described for the fetal CD5+ cells or B1 cells. Besides mantle cell lymphoma with classic histological features, a morphological variant of mantle cell lymphoma with blastic features and a more aggressive clinical course has been described. To investigate whether this variant is closely related, by the cell of origin, to typical cases, we analysed the presence and the pattern of somatic mutations of the VH genes in a series of nine cases diagnosed as such. Our cases of blastic mantle cell lymphomas rearrange most frequently VH4 and VH3 family genes. In three cases there was a complete homology to published germline genes, and a near complete homology was documented in another three. In contrast, the remaining three cases showed somatic mutations in their rearranged VH genes. Mutation analysis revealed evidence for antigen selection in one of these three cases. Taken together, these data are similar to those of normal adult-type B1 cells and those described for chronic lymphocytic leukaemia (CLL) but slightly different to those reported for classic mantle cell lymphoma. It is likely that blastic mantle cell lymphoma as well as CLL originates from adult-type B1 cells. More cases will need to be studied to determine whether classic mantle cell lymphoma is different from the blastic subtype and if it arises from fetal-type B1 cells.
authors.affiliation: Department of Pathology II, University Hospitals, Leuven, Belgium.
authors.forename: S
authors.initials: S
authors.lastname: Pittaluga
authors.forename: A
authors.initials: A
authors.lastname: Tierens
authors.forename: M
authors.initials: M
authors.lastname: Pinyol
authors.forename: E
authors.initials: E
authors.lastname: Campo
authors.forename: J
authors.initials: J
authors.lastname: Delabie
authors.forename: C
authors.initials: C
authors.lastname: De Wolf-Peeters
mesh_terms: D000595:Amino Acid Sequence; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain; D006801:Humans; D008228:Lymphoma, Non-Hodgkin / Q000235:genetics*; D008969:Molecular Sequence Data; D009154:Mutation; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D017421:Sequence Analysis