title: A limited role for TP53 mutation in the transformation of follicular lymphoma to diffuse large B-cell lymphoma.
abstract: The role of TP53 mutation in transformation of follicular lymphoma (FL) to diffuse large B-cell lymphoma (t-FL) was examined in a panel of 91 lymph node biopsies derived from 29 patients pre- and post-transformation. The entire TP53 coding sequence was screened and immunocytochemistry performed to determine expression of p53 and its key regulator MDM2. A total of 10 mutations were detected in eight patients (28%), although none were present at FL diagnosis. Mutations were not detected solely at the time of transformation; in three patients, mutated TP53 arose in at least one antecedent FL sample (6 months, 2.5 years and 4 years prior to transformation). Loss of heterozygosity at the TP53 locus occurred in 2/20 informative patients (only in t-FL samples). p53 staining was positive in 82% (9/11) of available biopsies with a missense mutation, and negative in 71% (45/63) with wtTP53. MDM2 expression was significantly higher in t-FL samples (mean 72% positive; 95% confidence interval (95% CI) 68-76%) than FL (mean 58% positive; 95% CI 54-62%) (P<0.001) but did not correlate with TP53 status. TP53 mutation has only a limited role in the transformation of FL, exerting a heterogeneous influence upon phenotypic change. In contrast, dysregulation of MDM2 is frequent and may provide a more rational therapeutic target..
authors.affiliation: Cancer Research UK Medical Oncology Unit, Bart's and The Royal London School of Medicine and Dentistry, London, UK. Andrew.J.Davies@cancer.org.uk
authors.forename: A J
authors.initials: AJ
authors.lastname: Davies
authors.forename: A M
authors.initials: AM
authors.lastname: Lee
authors.forename: C
authors.initials: C
authors.lastname: Taylor
authors.forename: A J
authors.initials: AJ
authors.lastname: Clear
authors.forename: L K
authors.initials: LK
authors.lastname: Goff
authors.forename: S
authors.initials: S
authors.lastname: Iqbal
authors.forename: D
authors.initials: D
authors.lastname: Cuthbert-Heavens
authors.forename: M
authors.initials: M
authors.lastname: Calaminici
authors.forename: A J
authors.initials: AJ
authors.lastname: Norton
authors.forename: T A
authors.initials: TA
authors.lastname: Lister
authors.forename: J
authors.initials: J
authors.lastname: Fitzgibbon
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008198:Lymph Nodes / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000473:pathology; D008224:Lymphoma, Follicular / Q000473:pathology*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology*; D009154:Mutation; D020125:Mutation, Missense; D009363:Neoplasm Proteins / Q000032:analysis; D009687:Nuclear Proteins / Q000032:analysis*; D011518:Proto-Oncogene Proteins / Q000032:analysis*; D051736:Proto-Oncogene Proteins c-mdm2; D016159:Tumor Suppressor Protein p53 / Q000032:analysis / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins; D009687:Nuclear Proteins; D011518:Proto-Oncogene Proteins; D016159:Tumor Suppressor Protein p53; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2