Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells

Sandeep S. Dave, George Wright, Bruce Tan, Andreas Rosenwald, Randy D. Gascoyne, Wing C. Chan, Richard I. Fisher, Rita M. Braziel, Lisa M Rimsza, Thomas M. Grogan, Thomas P Miller, Michael LeBlanc, Timothy C. Greiner, Dennis D. Weisenburger, James C. Lynch, Julie Vose, James O. Armitage, Erlend B. Smeland, Stein Kvaloy, Harald HolteJan Delabie, Joseph M. Connors, Peter M. Lansdorp, Qin Ouyang, T. Andrew Lister, Andrew J. Davies, Andrew J. Norton, H. Konrad Muller-Hermelink, German Ott, Elias Campo, Emilio Montserrat, Wyndham H. Wilson, Elaine S. Jaffe, Richard Simon, Liming Yang, John Powell, Hong Zhao, Neta Goldschmidt, Michael Chiorazzi, Louis M. Staudt

Research output: Contribution to journalArticle

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Abstract

BACKGROUND: Patients with follicular lymphoma may survive for periods of less than 1 year to more than 20 years after diagnosis. We used gene-expression profiles of tumor-biopsy specimens obtained at diagnosis to develop a molecular predictor of the length of survival. METHODS: Gene-expression profiling was performed on 191 biopsy specimens obtained from patients with untreated follicular lymphoma. Supervised methods were used to discover expression patterns associated with the length of survival in a training set of 95 specimens. A molecular predictor of survival was constructed from these genes and validated in an independent test set of 96 specimens. RESULTS: Individual genes that predicted the length of survival were grouped into gene-expression signatures on the basis of their expression in the training set, and two such signatures were used to construct a survival predictor. The two signatures allowed patients with specimens in the test set to be divided into four quartiles with widely disparate median lengths of survival (13.6, 11.1, 10.8, and 3.9 years), independently of clinical prognostic variables. Flow cytometry showed that these signatures reflected gene expression by nonmalignant tumor-infiltrating immune cells. CONCLUSIONS: The length of survival among patients with follicular lymphoma correlates with the molecular features of nonmalignant immune cells present in the tumor at diagnosis.

Original languageEnglish (US)
Pages (from-to)2159-2169
Number of pages11
JournalNew England Journal of Medicine
Volume351
Issue number21
DOIs
StatePublished - Nov 18 2004

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Follicular Lymphoma
Survival
Transcriptome
Neoplasms
Biopsy
Gene Expression Profiling
Genes
Flow Cytometry

ASJC Scopus subject areas

  • Medicine(all)

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Dave, S. S., Wright, G., Tan, B., Rosenwald, A., Gascoyne, R. D., Chan, W. C., ... Staudt, L. M. (2004). Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. New England Journal of Medicine, 351(21), 2159-2169. https://doi.org/10.1056/NEJMoa041869

Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. / Dave, Sandeep S.; Wright, George; Tan, Bruce; Rosenwald, Andreas; Gascoyne, Randy D.; Chan, Wing C.; Fisher, Richard I.; Braziel, Rita M.; Rimsza, Lisa M; Grogan, Thomas M.; Miller, Thomas P; LeBlanc, Michael; Greiner, Timothy C.; Weisenburger, Dennis D.; Lynch, James C.; Vose, Julie; Armitage, James O.; Smeland, Erlend B.; Kvaloy, Stein; Holte, Harald; Delabie, Jan; Connors, Joseph M.; Lansdorp, Peter M.; Ouyang, Qin; Lister, T. Andrew; Davies, Andrew J.; Norton, Andrew J.; Muller-Hermelink, H. Konrad; Ott, German; Campo, Elias; Montserrat, Emilio; Wilson, Wyndham H.; Jaffe, Elaine S.; Simon, Richard; Yang, Liming; Powell, John; Zhao, Hong; Goldschmidt, Neta; Chiorazzi, Michael; Staudt, Louis M.

In: New England Journal of Medicine, Vol. 351, No. 21, 18.11.2004, p. 2159-2169.

Research output: Contribution to journalArticle

Dave, SS, Wright, G, Tan, B, Rosenwald, A, Gascoyne, RD, Chan, WC, Fisher, RI, Braziel, RM, Rimsza, LM, Grogan, TM, Miller, TP, LeBlanc, M, Greiner, TC, Weisenburger, DD, Lynch, JC, Vose, J, Armitage, JO, Smeland, EB, Kvaloy, S, Holte, H, Delabie, J, Connors, JM, Lansdorp, PM, Ouyang, Q, Lister, TA, Davies, AJ, Norton, AJ, Muller-Hermelink, HK, Ott, G, Campo, E, Montserrat, E, Wilson, WH, Jaffe, ES, Simon, R, Yang, L, Powell, J, Zhao, H, Goldschmidt, N, Chiorazzi, M & Staudt, LM 2004, 'Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells', New England Journal of Medicine, vol. 351, no. 21, pp. 2159-2169. https://doi.org/10.1056/NEJMoa041869
Dave, Sandeep S. ; Wright, George ; Tan, Bruce ; Rosenwald, Andreas ; Gascoyne, Randy D. ; Chan, Wing C. ; Fisher, Richard I. ; Braziel, Rita M. ; Rimsza, Lisa M ; Grogan, Thomas M. ; Miller, Thomas P ; LeBlanc, Michael ; Greiner, Timothy C. ; Weisenburger, Dennis D. ; Lynch, James C. ; Vose, Julie ; Armitage, James O. ; Smeland, Erlend B. ; Kvaloy, Stein ; Holte, Harald ; Delabie, Jan ; Connors, Joseph M. ; Lansdorp, Peter M. ; Ouyang, Qin ; Lister, T. Andrew ; Davies, Andrew J. ; Norton, Andrew J. ; Muller-Hermelink, H. Konrad ; Ott, German ; Campo, Elias ; Montserrat, Emilio ; Wilson, Wyndham H. ; Jaffe, Elaine S. ; Simon, Richard ; Yang, Liming ; Powell, John ; Zhao, Hong ; Goldschmidt, Neta ; Chiorazzi, Michael ; Staudt, Louis M. / Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells. In: New England Journal of Medicine. 2004 ; Vol. 351, No. 21. pp. 2159-2169.
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abstract = "BACKGROUND: Patients with follicular lymphoma may survive for periods of less than 1 year to more than 20 years after diagnosis. We used gene-expression profiles of tumor-biopsy specimens obtained at diagnosis to develop a molecular predictor of the length of survival. METHODS: Gene-expression profiling was performed on 191 biopsy specimens obtained from patients with untreated follicular lymphoma. Supervised methods were used to discover expression patterns associated with the length of survival in a training set of 95 specimens. A molecular predictor of survival was constructed from these genes and validated in an independent test set of 96 specimens. RESULTS: Individual genes that predicted the length of survival were grouped into gene-expression signatures on the basis of their expression in the training set, and two such signatures were used to construct a survival predictor. The two signatures allowed patients with specimens in the test set to be divided into four quartiles with widely disparate median lengths of survival (13.6, 11.1, 10.8, and 3.9 years), independently of clinical prognostic variables. Flow cytometry showed that these signatures reflected gene expression by nonmalignant tumor-infiltrating immune cells. CONCLUSIONS: The length of survival among patients with follicular lymphoma correlates with the molecular features of nonmalignant immune cells present in the tumor at diagnosis.",
author = "Dave, {Sandeep S.} and George Wright and Bruce Tan and Andreas Rosenwald and Gascoyne, {Randy D.} and Chan, {Wing C.} and Fisher, {Richard I.} and Braziel, {Rita M.} and Rimsza, {Lisa M} and Grogan, {Thomas M.} and Miller, {Thomas P} and Michael LeBlanc and Greiner, {Timothy C.} and Weisenburger, {Dennis D.} and Lynch, {James C.} and Julie Vose and Armitage, {James O.} and Smeland, {Erlend B.} and Stein Kvaloy and Harald Holte and Jan Delabie and Connors, {Joseph M.} and Lansdorp, {Peter M.} and Qin Ouyang and Lister, {T. Andrew} and Davies, {Andrew J.} and Norton, {Andrew J.} and Muller-Hermelink, {H. Konrad} and German Ott and Elias Campo and Emilio Montserrat and Wilson, {Wyndham H.} and Jaffe, {Elaine S.} and Richard Simon and Liming Yang and John Powell and Hong Zhao and Neta Goldschmidt and Michael Chiorazzi and Staudt, {Louis M.}",
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T1 - Prediction of survival in follicular lymphoma based on molecular features of tumor-infiltrating immune cells

AU - Dave, Sandeep S.

AU - Wright, George

AU - Tan, Bruce

AU - Rosenwald, Andreas

AU - Gascoyne, Randy D.

AU - Chan, Wing C.

AU - Fisher, Richard I.

AU - Braziel, Rita M.

AU - Rimsza, Lisa M

AU - Grogan, Thomas M.

AU - Miller, Thomas P

AU - LeBlanc, Michael

AU - Greiner, Timothy C.

AU - Weisenburger, Dennis D.

AU - Lynch, James C.

AU - Vose, Julie

AU - Armitage, James O.

AU - Smeland, Erlend B.

AU - Kvaloy, Stein

AU - Holte, Harald

AU - Delabie, Jan

AU - Connors, Joseph M.

AU - Lansdorp, Peter M.

AU - Ouyang, Qin

AU - Lister, T. Andrew

AU - Davies, Andrew J.

AU - Norton, Andrew J.

AU - Muller-Hermelink, H. Konrad

AU - Ott, German

AU - Campo, Elias

AU - Montserrat, Emilio

AU - Wilson, Wyndham H.

AU - Jaffe, Elaine S.

AU - Simon, Richard

AU - Yang, Liming

AU - Powell, John

AU - Zhao, Hong

AU - Goldschmidt, Neta

AU - Chiorazzi, Michael

AU - Staudt, Louis M.

PY - 2004/11/18

Y1 - 2004/11/18

N2 - BACKGROUND: Patients with follicular lymphoma may survive for periods of less than 1 year to more than 20 years after diagnosis. We used gene-expression profiles of tumor-biopsy specimens obtained at diagnosis to develop a molecular predictor of the length of survival. METHODS: Gene-expression profiling was performed on 191 biopsy specimens obtained from patients with untreated follicular lymphoma. Supervised methods were used to discover expression patterns associated with the length of survival in a training set of 95 specimens. A molecular predictor of survival was constructed from these genes and validated in an independent test set of 96 specimens. RESULTS: Individual genes that predicted the length of survival were grouped into gene-expression signatures on the basis of their expression in the training set, and two such signatures were used to construct a survival predictor. The two signatures allowed patients with specimens in the test set to be divided into four quartiles with widely disparate median lengths of survival (13.6, 11.1, 10.8, and 3.9 years), independently of clinical prognostic variables. Flow cytometry showed that these signatures reflected gene expression by nonmalignant tumor-infiltrating immune cells. CONCLUSIONS: The length of survival among patients with follicular lymphoma correlates with the molecular features of nonmalignant immune cells present in the tumor at diagnosis.

AB - BACKGROUND: Patients with follicular lymphoma may survive for periods of less than 1 year to more than 20 years after diagnosis. We used gene-expression profiles of tumor-biopsy specimens obtained at diagnosis to develop a molecular predictor of the length of survival. METHODS: Gene-expression profiling was performed on 191 biopsy specimens obtained from patients with untreated follicular lymphoma. Supervised methods were used to discover expression patterns associated with the length of survival in a training set of 95 specimens. A molecular predictor of survival was constructed from these genes and validated in an independent test set of 96 specimens. RESULTS: Individual genes that predicted the length of survival were grouped into gene-expression signatures on the basis of their expression in the training set, and two such signatures were used to construct a survival predictor. The two signatures allowed patients with specimens in the test set to be divided into four quartiles with widely disparate median lengths of survival (13.6, 11.1, 10.8, and 3.9 years), independently of clinical prognostic variables. Flow cytometry showed that these signatures reflected gene expression by nonmalignant tumor-infiltrating immune cells. CONCLUSIONS: The length of survival among patients with follicular lymphoma correlates with the molecular features of nonmalignant immune cells present in the tumor at diagnosis.

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