title: The presence of TP53 mutation at diagnosis of follicular lymphoma identifies a high-risk group of patients with shortened time to disease progression and poorer overall survival.
abstract: The International Prognostic Index and the Follicular Lymphoma International Prognostic Index are widely used for the risk assessment of follicular lymphoma (FL). Although molecular studies have provided insight into the biology of FL, no molecular marker has impacted on treatment stratification. Because TP53 mutations are associated with poor prognosis in hematologic malignancies, we investigated the prognostic value of TP53 mutation at diagnosis in FL. Heterozygous TP53 mutation was detected in 12 of 185 (6%) analyzed cases. Mutation was associated with older age (P = .02) and higher International Prognostic Index score (P = .04). On multivariate analysis, TP53 mutation correlated with shorter progression-free survival (P < .001) and overall survival (P = .009). TP53 mutation was associated with low expression of the immune-response 1 gene expression signature (P = .016) and with an unfavorable gene expression-based survival predictor score (P < .001), demonstrating for the first time that molecular features of the malignant cell may correlate with the nature of the immune response in FL.
authors.affiliation: Centre for Medical Oncology, Barts and the London School of Medicine, London, United Kingdom. derville.oshea@cancer.org.uk
authors.forename: Derville
authors.initials: D
authors.lastname: O'Shea
authors.forename: Ciarán
authors.initials: C
authors.lastname: O'Riain
authors.forename: Claire
authors.initials: C
authors.lastname: Taylor
authors.forename: Rachel
authors.initials: R
authors.lastname: Waters
authors.forename: Emanuela
authors.initials: E
authors.lastname: Carlotti
authors.forename: Finlay
authors.initials: F
authors.lastname: Macdougall
authors.forename: John
authors.initials: J
authors.lastname: Gribben
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.forename: Lisa M
authors.initials: LM
authors.lastname: Rimsza
authors.forename: Erlend B
authors.initials: EB
authors.lastname: Smeland
authors.forename: Nathalie
authors.initials: N
authors.lastname: Johnson
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: Timothy C
authors.initials: TC
authors.lastname: Greiner
authors.forename: Wing C
authors.initials: WC
authors.lastname: Chan
authors.forename: Randy D
authors.initials: RD
authors.lastname: Gascoyne
authors.forename: George
authors.initials: G
authors.lastname: Wright
authors.forename: Louis M
authors.initials: LM
authors.lastname: Staudt
authors.forename: T Andrew
authors.initials: TA
authors.lastname: Lister
authors.forename: Jude
authors.initials: J
authors.lastname: Fitzgibbon
mesh_terms: D000368:Aged; D018450:Disease Progression; D018572:Disease-Free Survival; D016158:Genes, p53; D006579:Heterozygote; D006801:Humans; D008224:Lymphoma, Follicular / Q000175:diagnosis* / Q000235:genetics* / Q000401:mortality; D008875:Middle Aged; D015999:Multivariate Analysis; D009154:Mutation; D011379:Prognosis; D012306:Risk; D013997:Time Factors; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism
chemical_list: D016159:Tumor Suppressor Protein p53