Genomic and gene expression profiling defines indolent forms of mantle cell lymphoma

Verònica Fernàndez, Olga Salamero, Blanca Espinet, Francesc Solé, Cristina Royo, Alba Navarro, Francisca Camacho, Sílvia Beà, Elena Hartmann, Virginia Amador, Luis Hernández, Claudio Agostinelli, Rachel L. Sargent, Maria Rozman, Marta Aymerich, Dolors Colomer, Neus Villamor, Steven H. Swerdlow, Stefano A. Pileri, Francesc BoschMiguel A. Piris, Emili Montserrat, German Ott, Andreas Rosenwald, Armando López-Guillermo, Pedro Jares, Sergi Serrano, Elías Campo

Research output: Contribution to journalArticle

Abstract

Mantle cell lymphoma (MCL) is typically a very aggressive disease with poor outcomes, but some cases display an indolent behavior that might not necessitate treatment at diagnosis. To define molecular criteria that might permit recognition of such cases, we compared the clinicopathologic features, gene expression, and genomic profile of patients who had indolent or conventional disease (iMCL or cMCL). Patients with iMCL displayed nonnodal leukemic disease with predominantly hypermutated IGVH and noncomplex karyotypes. iMCL and cMCL shared a common gene expression profile that differed from other leukemic lymphoid neoplasms. However, we identified a signature of 13 genes that was highly expressed in cMCL but underexpressed in iMCL. SOX11 was notable in this signature and we confirmed a restriction of SOX11 protein expression to cMCL. To validate the potential use of SOX11 as a biomarker for cMCL, we evaluated SOX11 protein expression in an independent series of 112 cases of MCL. Fifteen patients with SOX11-negative tumors exhibited more frequent nonnodal presentation and better survival compared with 97 patients with SOX11-positive MCL (5-year overall survival of 78% versus 36%, respectively; P = 0.001). In conclusion, we defined nonnodal presentation, predominantly hypermutated IGVH, lack of genomic complexity, and absence of SOX11 expression as qualities of a specific subtype of iMCL with excellent outcomes that might be managed more conservatively than cMCL.

Original languageEnglish
Pages (from-to)1408-1418
Number of pages11
JournalCancer Research
Volume70
Issue number4
DOIs
Publication statusPublished - Feb 15 2010

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ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Fernàndez, V., Salamero, O., Espinet, B., Solé, F., Royo, C., Navarro, A., Camacho, F., Beà, S., Hartmann, E., Amador, V., Hernández, L., Agostinelli, C., Sargent, R. L., Rozman, M., Aymerich, M., Colomer, D., Villamor, N., Swerdlow, S. H., Pileri, S. A., ... Campo, E. (2010). Genomic and gene expression profiling defines indolent forms of mantle cell lymphoma. Cancer Research, 70(4), 1408-1418. https://doi.org/10.1158/0008-5472.CAN-09-3419