Genomic and gene expression profiling defines indolent forms of mantle cell lymphoma.
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.
Fernàndez
Verònica
V
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.
Salamero
Olga
O
Espinet
Blanca
B
Solé
Francesc
F
Royo
Cristina
C
Navarro
Alba
A
Camacho
Francisca
F
Beà
Sílvia
S
Hartmann
Elena
E
Amador
Virginia
V
Hernández
Luis
L
Agostinelli
Claudio
C
Sargent
Rachel L
RL
Rozman
Maria
M
Aymerich
Marta
M
Colomer
Dolors
D
Villamor
Neus
N
Swerdlow
Steven H
SH
Pileri
Stefano A
SA
Bosch
Francesc
F
Piris
Miguel A
MA
Montserrat
Emili
E
Ott
German
G
Rosenwald
Andreas
A
López-Guillermo
Armando
A
Jares
Pedro
P
Serrano
Sergi
S
Campo
Elías
E
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
C097473:SOX11 protein, human; D055751:SOXC Transcription Factors