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Blood, 15 October 2008, Vol. 112, No. 8, pp. 3126-3129.
Prepublished online as a Blood First Edition Paper on July 15, 2008; DOI 10.1182/blood-2008-05-154013.
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Submitted May 14, 2008
Accepted July 10, 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 a poorer overall survival
Derville O'Shea*, Ciaran 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 C. Greiner, Wing C. Chan, Randy D. Gascoyne, George Wright, Louis M. Staudt, Thomas A. Lister, and Jude Fitzgibbon
Centre for Medical Oncology, Barts and the London School of Medicine, London, United Kingdom
Mutation Detection Facility, St James's University Hospital, Leeds, United Kingdom
Centre for Statistics in Medicine, Oxford University, Oxford, United Kingdom
Institute of Pathology, University of Wurzburg, Wurzburg, Germany
Department of Clinical Pathology, Robert-Bosch-Krankenhaus, Stuttgart, Germany
Department of Pathology and Arizona Cancer Center, University of Arizona, Tucson, United States
Department of Immunology, Institute for Cancer Research, Rikshospitalet University Hospital, Oslo, Norway
Department of Pathology and Division of Medical Oncology, British Columbia Cancer Agency, Vancouver, Canada
Hematopathology Section, Department of Pathology, Institut d'Investigacions Biomediques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain
Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, Nebraska, United States
Biometric Research Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States
Metabolism Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, United States
* Corresponding author; email: derville.oshea{at}cancer.org.uk.
The International Prognostic Index (IPI) and the Follicular Lymphoma (FL) IPI, (FLIPI) are widely used for the risk assessment of FL. Although molecular studies have provided insight into the biology of FL, no molecular marker has impacted on treatment stratification. As TP53 mutations are associated with poor prognosis in hematological malignancies we investigated the prognostic value of TP53 mutation at diagnosis in FL. Heterozygous TP53 mutation was detected in 12/185 (6%) analyzed cases. Mutation was associated with older age (p=0.02) and higher IPI score (p=0.04). On multivariate analysis TP53 mutation correlated with shorter progression free (p=0.0003) and overall survival (p=0.009). TP53 mutation was associated with low expression of the immune-response 1 gene expression signature (p=0.016) and with an unfavorable gene expression-based survival predictor score (p=0.001), 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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