TY - JOUR
T1 - Genomic and gene expression profiling defines indolent forms of mantle cell lymphoma
AU - Fernàndez, Verònica
AU - Salamero, Olga
AU - Espinet, Blanca
AU - Solé, Francesc
AU - Royo, Cristina
AU - Navarro, Alba
AU - Camacho, Francisca
AU - Beà, Sílvia
AU - Hartmann, Elena
AU - Amador, Virginia
AU - Hernández, Luis
AU - Agostinelli, Claudio
AU - Sargent, Rachel L.
AU - Rozman, Maria
AU - Aymerich, Marta
AU - Colomer, Dolors
AU - Villamor, Neus
AU - Swerdlow, Steven H.
AU - Pileri, Stefano A.
AU - Bosch, Francesc
AU - Piris, Miguel A.
AU - Montserrat, Emili
AU - Ott, German
AU - Rosenwald, Andreas
AU - López-Guillermo, Armando
AU - Jares, Pedro
AU - Serrano, Sergi
AU - Campo, Elías
PY - 2010/2/15
Y1 - 2010/2/15
N2 - 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.
AB - 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.
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U2 - 10.1158/0008-5472.CAN-09-3419
DO - 10.1158/0008-5472.CAN-09-3419
M3 - Article
C2 - 20124476
AN - SCOPUS:76749118059
VL - 70
SP - 1408
EP - 1418
JO - Journal of Cancer Research
JF - Journal of Cancer Research
SN - 0008-5472
IS - 4
ER -