title: Transformation of follicular lymphoma to diffuse large B-cell lymphoma may occur by divergent evolution from a common progenitor cell or by direct evolution from the follicular lymphoma clone.
abstract: To investigate the cell of origin linking follicular (FL) and transformed (t-FL) lymphomas, we analyzed the somatic hypermutation (SHM) pattern of the variable region of the immunoglobulin heavy gene (IgH-VH) in 18 sequential FL/t-FL samples and a father (donor) and son (recipient), who developed FL and t-FL, after transplantation. Genealogic trees showed a pattern compatible with a common progenitor cell (CPC) origin in 13 cases. The identification of the t-FL clonotype in the previous FL sample and of the putative CPC sequence in both the FL/t-FL biopsies showed that the intraclonal diversity of FL and t-FL germinal centers (GCs) is more intricate than previously described, and all 3 clonotypes (CPC, FL, t-FL) may occur simultaneously within the same lymph node. On the basis of the father/son model, this CPC must be long-lived, providing a possible explanation for the incurable nature of this disease.
authors.affiliation: Centre for Medical Oncology Laboratory, Barts and The London School of Medicine and Dentistry, London, United Kingdom. emanuela.carlotti@cancer.org.uk
authors.forename: Emanuela
authors.initials: E
authors.lastname: Carlotti
authors.forename: David
authors.initials: D
authors.lastname: Wrench
authors.forename: Janet
authors.initials: J
authors.lastname: Matthews
authors.forename: Sameena
authors.initials: S
authors.lastname: Iqbal
authors.forename: Andrew
authors.initials: A
authors.lastname: Davies
authors.forename: Andrew
authors.initials: A
authors.lastname: Norton
authors.forename: Jason
authors.initials: J
authors.lastname: Hart
authors.forename: Raymond
authors.initials: R
authors.lastname: Lai
authors.forename: Silvia
authors.initials: S
authors.lastname: Montoto
authors.forename: John G
authors.initials: JG
authors.lastname: Gribben
authors.forename: T Andrew
authors.initials: TA
authors.lastname: Lister
authors.forename: Jude
authors.initials: J
authors.lastname: Fitzgibbon
mesh_terms: D001706:Biopsy; D016026:Bone Marrow Transplantation; D002471:Cell Transformation, Neoplastic / Q000235:genetics* / Q000276:immunology; D002999:Clone Cells / Q000276:immunology / Q000473:pathology; D018858:Germinal Center / Q000473:pathology; D006801:Humans; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000473:pathology* / Q000628:therapy; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000473:pathology*; D008297:Male; D027041:Somatic Hypermutation, Immunoglobulin; D013234:Stem Cells / Q000276:immunology / Q000473:pathology*