Indexat a

Llicència i ús

Citacions

Cited 96 times in

Cited 90 times in

Cited 6 times in

Cited 98 times in

Altmetrics

Grant support

Supported by a National Cancer Institute Strategic Partnering to Evaluate Cancer Signatures (SPECS II) grant (5U01CA157581-05) and in part by the Leukemia and Lymphoma Society of Canada and the Terry Fox Research Institute (Grant No. 1061). The BC Cancer Agency Centre for Lymphoid Cancer clinical database is supported by Roche. The research at the City of Hope was supported in part by the National Cancer Institute (award No. P30CA033572). The research at the University of Nebraska Medical Center was supported by the Fred & Pamela Buffett Cancer Center's National Cancer Institute Cancer Center Support Grant (P30CA036727). Research at Oslo University Hospital was supported by The Research Council of Norway's Centres of Excellence Scheme Research Council (Project No. 179571). D.W.S. is supported by the BC Cancer Agency. P.A.'s fellowship at the BC Cancer Agency was supported by funds from Vall d'Hebron University Hospital, Barcelona, Spain. G.W.W. is supported by the Division of Cancer Treatment and Diagnosis, National Cancer Institute, Bethesda, MD. A.M. is supported by fellowship awards from the Mildred-Scheel-Cancer Foundation, the Michael Smith Foundation for Health Research, and Lymphoma Canada. G.O. is supported by the Robert-Bosch-Foundation, Stuttgart, Germany. H.H. is supported by the Norwegian Cancer Society. E.S.J. and L.M.S. are supported by the Center for Cancer Research, National Cancer Institute, Bethesda, MD. C.S. is the recipient of a Career Investigator Award from the Michael Smith Foundation for Health Research. J.M.C. received research funding support from the Terry Fox Research Institute, Genome Canada, Genome British Columbia, the Canadian Institutes for Health Research, and the BC Cancer Foundation. E.C. was supported in part by the Ministerio de Economia y Competitividad Grant No. SAF2015-64885-R, Generalitat de Catalunya Suport Grups de Recerca 2014-SGR-795, and Institucio Catalana de Recerca i Estudis Avancats. L.M.R.'s laboratory infrastructure and tissue banking are supported by awards from the National Cancer Institute Specialized Program in Research Excellence (5P50CA097274) and the Mayo Comprehensive Cancer Center (5P30CA015083).

Anàlisi d'autories institucional

Compartir

New Molecular Assay for the Proliferation Signature in Mantle Cell Lymphoma Applicable to Formalin-Fixed Paraffin-Embedded Biopsies.

Publicat a:Journal Of Clinical Oncology. 35 (15): 1668-+ - 2017-05-20 35(15), DOI: 10.1200/jco.2016.70.7901

Autors: Scott, David W; Abrisqueta, Pau; Wright, George W; Slack, Graham W; Mottok, Anja; Villa, Diego; Jares, Pedro; Rauert-Wunderlich, Hilka; Royo, Cristina; Clot, Guillem; Pinyol, Magda; Boyle, Merrill; Chan, Fong Chun; Braziel, Rita M; Chan, Wing C; Weisenburger, Dennis D; Cook, James R; Greiner, Timothy C; Fu, Kai; Ott, German; Delabie, Jan; Smeland, Erlend B; Holte, Harald; Jaffe, Elaine S; Steidl, Christian; Connors, Joseph M; Gascoyne, Randy D; Rosenwald, Andreas; Staudt, Louis M; Campo, Elias; Rimsza, Lisa M

Afiliacions

Resum

Purpose Mantle cell lymphoma is an aggressive B-cell neoplasm that displays heterogeneous outcomes after treatment. In 2003, the Lymphoma/Leukemia Molecular Profiling Project described a powerful biomarker-the proliferation signature-using gene expression in fresh frozen material. Herein, we describe the training and validation of a new assay that measures the proliferation signature in RNA derived from routinely available formalin-fixed paraffin-embedded (FFPE) biopsies. Methods Forty-seven FFPE biopsies were used to train an assay on the NanoString platform, using microarray gene expression data of matched fresh frozen biopsies as a gold standard. The locked assay was applied to pretreatment FFPE lymph node biopsies from an independent cohort of 110 patients uniformly treated with rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone. Seventeen biopsies were tested across three laboratories to assess assay reproducibility. Results The MCL35 assay, which contained a 17-gene proliferation signature, yielded gene expression of sufficient quality to assign an assay score and risk group in 108 (98%) of 110 archival FFPE biopsies. The MCL35 assay assigned patients to high-risk (26%), standard-risk (29%), and low-risk (45%) groups, with different lengths of overall survival (OS): a median of 1.1, 2.6, and 8.6 years, respectively (log-rank for trend, P < .001). In multivariable analysis, these risk groups and the Mantle Cell Lymphoma International Prognostic Index were independently associated with OS ( P < .001 for both variables). Concordance of risk assignment across the three independent laboratories was 100%. Conclusion The newly developed and validated MCL35 assay for FFPE biopsies uses the proliferation signature to define groups of patients with significantly different OS independent of the Mantle Cell Lymphoma International Prognostic Index. Importantly, the analytic and clinical validity of this assay defines it as a reliable biomarker to support risk-adapted clinical trials.

Paraules clau