title: CCND2 rearrangements are the most frequent genetic events in cyclin D1(-) mantle cell lymphoma.
abstract: Cyclin D1(-) mantle cell lymphomas (MCLs) are not well characterized, in part because of the difficulties in their recognition. SOX11 has been identified recently as a reliable biomarker of MCL that is also expressed in the cyclin D1(-) variant. We investigated 40 lymphomas with MCL morphology and immunophenotype that were negative for cyclin D1 expression/t(11;14)(q13;q32) but positive for SOX11. These tumors presented clinically with generalized lymphadenopathy, advanced stage, and poor outcome (5-year overall survival, 48%). Chromosomal rearrangements of the CCND2 locus were detected in 55% of the cases, with an IG gene as partner in 18 of 22, in particular with light chains (10 IGK@ and 5 IGL@). No mutations in the phosphorylation motifs of CCND1, CCND2, or CCND3 were detected. The global genomic profile and the high complexity of the 32 cyclin D1(-) SOX11(+) MCL patients analyzed by copy number arrays were similar to the conventional cyclin D1/SOX11 MCL. 17p deletions and high Ki67 expression conferred a significantly worse outcome for the patients. This comprehensive characterization of a large series of cyclin D1(-) MCL patients indicates that these tumors are clinically and biologically similar to the conventional cyclin D1(+) MCL and provides a basis for the proper identification and clinical management of these patients.
authors.affiliation: Department of Pathology, Hematopathology Unit, Hospital Clínic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Barcelona, Spain.
authors.forename: Itziar
authors.initials: I
authors.lastname: Salaverria
authors.forename: Cristina
authors.initials: C
authors.lastname: Royo
authors.forename: Alejandra
authors.initials: A
authors.lastname: Carvajal-Cuenca
authors.forename: Guillem
authors.initials: G
authors.lastname: Clot
authors.forename: Alba
authors.initials: A
authors.lastname: Navarro
authors.forename: Alejandra
authors.initials: A
authors.lastname: Valera
authors.forename: Joo Y
authors.initials: JY
authors.lastname: Song
authors.forename: Renata
authors.initials: R
authors.lastname: Woroniecka
authors.forename: Grzegorz
authors.initials: G
authors.lastname: Rymkiewicz
authors.forename: Wolfram
authors.initials: W
authors.lastname: Klapper
authors.forename: Elena M
authors.initials: EM
authors.lastname: Hartmann
authors.forename: Pierre
authors.initials: P
authors.lastname: Sujobert
authors.forename: Iwona
authors.initials: I
authors.lastname: Wlodarska
authors.forename: Judith A
authors.initials: JA
authors.lastname: Ferry
authors.forename: Philippe
authors.initials: P
authors.lastname: Gaulard
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: Lopez-Guillermo
authors.forename: Leticia
authors.initials: L
authors.lastname: Quintanilla-Martinez
authors.forename: Nancy L
authors.initials: NL
authors.lastname: Harris
authors.forename: Elaine S
authors.initials: ES
authors.lastname: Jaffe
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: Elias
authors.initials: E
authors.lastname: Campo
authors.forename: Sílvia
authors.initials: S
authors.lastname: Beà
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019938:Cyclin D1 / Q000235:genetics* / Q000378:metabolism; D056742:Cyclin D2 / Q000235:genetics* / Q000378:metabolism; D056743:Cyclin D3 / Q000235:genetics / Q000378:metabolism; D056915:DNA Copy Number Variations / Q000235:genetics; D004252:DNA Mutational Analysis; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D020522:Lymphoma, Mantle-Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D008875:Middle Aged; D012333:RNA, Messenger / Q000235:genetics; D055751:SOXC Transcription Factors / Q000235:genetics / Q000378:metabolism; D014178:Translocation, Genetic / Q000235:genetics
chemical_list: C530104:CCND1 protein, human; C080336:CCND2 protein, human; C534696:CCND3 protein, human; D056742:Cyclin D2; D056743:Cyclin D3; D012333:RNA, Messenger; C097473:SOX11 protein, human; D055751:SOXC Transcription Factors; D019938:Cyclin D1