title: Quantifying the role of aberrant somatic hypermutation in transformation of follicular lymphoma.
abstract: Somatic hypermutation (SHM) aberrantly targets proto-oncogenes in various non-Hodgkin's lymphoma. To test the association of SHM with transformation of follicular lymphoma (FL), we sequenced mutational hot spots in five proto-oncogenes (BCL6, PAX5, RHOH, MYC and PIM1) in 32 low-grade FL (lgFL) with follicular histology and 26 transformed FL (tFL) with diffuse large cell histology. No difference was detected in the fraction of specimens mutated (75% of lgFL and 77% of tFL) or in the mutation load (0.08 for lgFL vs. 0.06 mutations/100 bp/allele for tFL). Serial specimens were examined from 25 patients showing stable low-grade FL (slgFL; n=6) or a low-grade FL that later transformed into diffuse large cell lymphoma (tFL; n=19). slgFL and tFL patients accumulated similar numbers of mutations in the interval between biopsies. These data indicate that mutations attributable to aberrant SHM occur with similar frequency in low-grade and transformed FL; transformation is not associated with a higher rate of aberrant SHM. Moreover, the frequency of mutations attributable to aberrant SHM in tFL was significantly lower than that reported for de novo diffuse large B cell lymphoma, suggesting differing oncogenic mechanisms in transformed follicular lymphoma and de novo diffuse large B cell lymphoma.
authors.affiliation: Department of Pathology and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
authors.forename: Anna Margrét
authors.initials: AM
authors.lastname: Halldórsdóttir
authors.forename: Margareta
authors.initials: M
authors.lastname: Frühwirth
authors.forename: Alexander
authors.initials: A
authors.lastname: Deutsch
authors.forename: Ariane
authors.initials: A
authors.lastname: Aigelsreiter
authors.forename: Christine
authors.initials: C
authors.lastname: Beham-Schmid
authors.forename: Bjarni A
authors.initials: BA
authors.lastname: Agnarsson
authors.forename: Peter
authors.initials: P
authors.lastname: Neumeister
authors.forename: W
authors.initials: W
authors.lastname: Richard Burack
mesh_terms: D002471:Cell Transformation, Neoplastic; D006801:Humans; D008224:Lymphoma, Follicular / Q000235:genetics / Q000473:pathology*; D009154:Mutation