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

Derville O'Shea, Ciarán O'Riain, Claire Taylor, Rachel Waters, Emanuela Carlotti, Finlay MacDougall, John Gribben, Andreas Rosenwald, German Ott, Lisa M. Rimsza, Erlend B. Smeland, Nathalie Johnson, Elias Campo, Timothy Charles Greiner, Wing C. Chan, Randy D. Gascoyne, George Wright, Louis M. Staudt, T. Andrew Lister, Jude Fitzgibbon

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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.

Original languageEnglish (US)
Pages (from-to)3126-3129
Number of pages4
JournalBlood
Volume112
Issue number8
DOIs
StatePublished - Oct 15 2008

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Follicular Lymphoma
Gene expression
Disease Progression
Mutation
Survival
Risk assessment
Hematologic Neoplasms
Transcriptome
Disease-Free Survival
Multivariate Analysis
Gene Expression

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cite this

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. / O'Shea, Derville; O'Riain, Ciarán; Taylor, Claire; Waters, Rachel; Carlotti, Emanuela; MacDougall, Finlay; Gribben, John; Rosenwald, Andreas; Ott, German; Rimsza, Lisa M.; Smeland, Erlend B.; Johnson, Nathalie; Campo, Elias; Greiner, Timothy Charles; Chan, Wing C.; Gascoyne, Randy D.; Wright, George; Staudt, Louis M.; Lister, T. Andrew; Fitzgibbon, Jude.

In: Blood, Vol. 112, No. 8, 15.10.2008, p. 3126-3129.

Research output: Contribution to journalArticle

O'Shea, D, O'Riain, C, Taylor, C, Waters, R, Carlotti, E, MacDougall, F, Gribben, J, Rosenwald, A, Ott, G, Rimsza, LM, Smeland, EB, Johnson, N, Campo, E, Greiner, TC, Chan, WC, Gascoyne, RD, Wright, G, Staudt, LM, Lister, TA & Fitzgibbon, J 2008, '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', Blood, vol. 112, no. 8, pp. 3126-3129. https://doi.org/10.1182/blood-2008-05-154013
O'Shea, Derville ; O'Riain, Ciarán ; Taylor, Claire ; Waters, Rachel ; Carlotti, Emanuela ; MacDougall, Finlay ; Gribben, John ; Rosenwald, Andreas ; Ott, German ; Rimsza, Lisa M. ; Smeland, Erlend B. ; Johnson, Nathalie ; Campo, Elias ; Greiner, Timothy Charles ; Chan, Wing C. ; Gascoyne, Randy D. ; Wright, George ; Staudt, Louis M. ; Lister, T. Andrew ; Fitzgibbon, Jude. / 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. In: Blood. 2008 ; Vol. 112, No. 8. pp. 3126-3129.
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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.",
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AU - Johnson, Nathalie

AU - Campo, Elias

AU - Greiner, Timothy Charles

AU - Chan, Wing C.

AU - Gascoyne, Randy D.

AU - Wright, George

AU - Staudt, Louis M.

AU - Lister, T. Andrew

AU - Fitzgibbon, Jude

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N2 - 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.

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