title: Genomic and gene expression profiling defines indolent forms of mantle cell lymphoma.
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.
authors.affiliation: Hematopathology Section, Department of Pathology, Hospital Clinic, Institut d'Investigacions Biomediques August Pi i Sunyer and Department of Hematology, Hospital Clinic, University of Barcelona, 08036 Barcelona, Spain.
authors.forename: Verònica
authors.initials: V
authors.lastname: Fernàndez
authors.forename: Olga
authors.initials: O
authors.lastname: Salamero
authors.forename: Blanca
authors.initials: B
authors.lastname: Espinet
authors.forename: Francesc
authors.initials: F
authors.lastname: Solé
authors.forename: Cristina
authors.initials: C
authors.lastname: Royo
authors.forename: Alba
authors.initials: A
authors.lastname: Navarro
authors.forename: Francisca
authors.initials: F
authors.lastname: Camacho
authors.forename: Sílvia
authors.initials: S
authors.lastname: Beà
authors.forename: Elena
authors.initials: E
authors.lastname: Hartmann
authors.forename: Virginia
authors.initials: V
authors.lastname: Amador
authors.forename: Luis
authors.initials: L
authors.lastname: Hernández
authors.forename: Claudio
authors.initials: C
authors.lastname: Agostinelli
authors.forename: Rachel L
authors.initials: RL
authors.lastname: Sargent
authors.forename: Maria
authors.initials: M
authors.lastname: Rozman
authors.forename: Marta
authors.initials: M
authors.lastname: Aymerich
authors.forename: Dolors
authors.initials: D
authors.lastname: Colomer
authors.forename: Neus
authors.initials: N
authors.lastname: Villamor
authors.forename: Steven H
authors.initials: SH
authors.lastname: Swerdlow
authors.forename: Stefano A
authors.initials: SA
authors.lastname: Pileri
authors.forename: Francesc
authors.initials: F
authors.lastname: Bosch
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Piris
authors.forename: Emili
authors.initials: E
authors.lastname: Montserrat
authors.forename: German
authors.initials: G
authors.lastname: Ott
authors.forename: Andreas
authors.initials: A
authors.lastname: Rosenwald
authors.forename: Armando
authors.initials: A
authors.lastname: López-Guillermo
authors.forename: Pedro
authors.initials: P
authors.lastname: Jares
authors.forename: Sergi
authors.initials: S
authors.lastname: Serrano
authors.forename: Elías
authors.initials: E
authors.lastname: Campo
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016000:Cluster Analysis; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics / Q000379:methods; D006801:Humans; D008207:Lymphatic Metastasis; D020522:Lymphoma, Mantle-Cell / Q000145:classification* / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D055751:SOXC Transcription Factors / Q000032:analysis / Q000235:genetics; D016019:Survival Analysis
chemical_list: C097473:SOX11 protein, human; D055751:SOXC Transcription Factors