IDIBAPS investigators describe the genetic profile of an uncommon subtype of mantle cell lymphoma improving its proper diagnosis

Mantle cell lymphoma (MCL)is a subtype of B-cell lymphoma that comprises about 6-7% of all non-Hodgkin's lymphoma cases. The main biomarker of this usually aggressive lymphoma is an alteration in Cyclin D1 expression. An article led by IDIBAPS investigators, and published in Blood(1), characterizes a new subtype of MCLs in which Cyclin D1 expression is not altered and offers clues to close different controversies about the genetics of the disease. Dr. Itziar Salaverria is the first author of the article, while the Miguel Servet investigator Dr. Sílvia Beà is the last one, both from the Human and experimental functional oncomorphology IDIBAPS team led by Dr. Elías Campo. Due to its significance, the article was highlighted by its editors as one of the "hottest" manuscripts to the media and selected for a comment (2) in the last issue of the Blood magazine.

Cyclin D1 negative MCLs are not easy to recognize and reliable criteria for their diagnosis are lacking. In this study, the IDIBAPS investigators collected samples from 40 patients with this uncommon form of lymphoma using SOX11 as a biomarker for the diagnosis. SOX11 is a neural transcription factor involved in central nervous system development identified recently as a reliable biomarker of MCL that is also expressed in the cyclin D1- variant. Centers from Germany, USA, Belgium, France and Poland participated in the collection of samples, which were centralized and analyzed at the IDIBAPS, including a comprehensive phenotypic, genetic and molecular characterization.

Chromosomal rearrangements of the CCND2 gene were detected in 55% of the cases. No mutations in the phosphorylation motifs of CCND1, CCND2, or CCND3 nor rearrangements of the CCND3 locus were detected. The profile of genetic alterations of these cases was similar to the Cyclin D1+ cases and the clinical behavior was highly aggressive, suggesting that the expression of SOX11 may have a role in the pathogenesis of this lymphoma. Additionally, 17p deletions and a high rate of proliferation conferred a significantly worse outcome for the patients.

As a whole, 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. It provides a basis for the proper identification and clinical management of these patients. The ongoing collaborative studies may provide new insights into driver genes in cases lacking Cyclin D1 or D2 rearrangements and also other marker mutations with diagnostic implications.

References:

(1) Itziar Salaverria, Cristina Royo, Alejandra Carvajal-Cuenca, Guillem Clot, Alba Navarro, Alejandra Valera, Joo Y. Song, Renata Woroniecka, Grzegorz Rymkiewicz, Wolfram Klapper, Elena M. Hartmann, Pierre Sujobert, Iwona Wlodarska, Judith A. Ferry, Philippe Gaulard, German Ott, Andreas Rosenwald, Armando Lopez-Guillermo, Leticia Quintanilla-Martinez, Nancy L. Harris, Elaine S. Jaffe, Reiner Siebert, Elias Campo, and Sílvia Beà. CCND2 rearrangements are the most frequent genetic events in cyclin D1- mantle cell lymphoma. Blood; vol. 121 no. 8 1394-1402. doi: 10.1182/blood-2012-08-452284

(2) Masao Seto. Cyclin D1-negative mantle cell lymphoma. Blood; vol. 121 no. 8 1249-1250. doi: 10.1182/blood-2013-01-475954

Foto source: Diario Médico