Whole genome copy number analysis in search of new prognostic biomarkers in first line treatment of mantle cell lymphoma. A study by the LYSA group

Mantle cell lymphoma (MCL) is a lymphoproliferative disorder characterized by the t(11;14)(q13;q32) CCND1/IGH translocation. This lymphoma is however extremely heterogeneous in terms of molecular alterations. Moreover, the course of the disease can vary greatly between indolent forms with slow progr...

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Published in:Hematological oncology 2020-10, Vol.38 (4), p.446-455
Main Authors: Le Bris, Yannick, Magrangeas, Florence, Moreau, Anne, Chiron, David, Guérin‐Charbonnel, Catherine, Theisen, Olivier, Pichon, Olivier, Canioni, Danielle, Burroni, Barbara, Maisonneuve, Hervé, Thieblemont, Catherine, Oberic, Lucie, Gyan, Emmanuel, Pellat‐Deceunynck, Catherine, Hermine, Olivier, Delfau‐Larue, Marie‐Hélène, Tessoulin, Benoît, Béné, Marie‐Christine, Minvielle, Stéphane, Le Gouill, Steven
Format: Article
Language:English
Subjects:
Abnormalities
Anomalies
Biomarkers
Cancer
CCND1/IGH
Copy number
copy number anomalies
Deoxyribonucleic acid
Diagnostic systems
DNA
Genomes
Health services
Heavy chains
Heterozygosity
Immunoglobulins
Impact analysis
Life Sciences
Loss of heterozygosity
Lymph nodes
Lymphocytes
Lymphoma
Mantle cell lymphoma
Medical prognosis
Multivariate analysis
p53 Protein
Paraffin
Paraffins
Patients
prognosis
Schedules
Single-nucleotide polymorphism
Translocation
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Description
Summary:Mantle cell lymphoma (MCL) is a lymphoproliferative disorder characterized by the t(11;14)(q13;q32) CCND1/IGH translocation. This lymphoma is however extremely heterogeneous in terms of molecular alterations. Moreover, the course of the disease can vary greatly between indolent forms with slow progression and aggressive conditions rapidly pejorative. The identification of early markers allowing to predict individual patients outcome has however been unsuccessful so far. The LyMa trial treated homogeneously a cohort of young MCL patients. This appeared as a good opportunity to search for biomarkers of response to therapy. DNA extracted from diagnostic paraffin‐embedded lymph node biopsies from 100 patients with newly diagnosed MCL, homogeneously treated in this prospective clinical trial, were investigated for copy number alterations and copy neutral loss of heterozygosity using the Oncoscan SNP‐array scanning the whole genome. An independent confirmatory cohort was used to strengthen the possibly relevant anomalies observed. Here we describe the recurrent anomalies identified with this technique. Deletions of 17p(TP53) and 9p(CDKN2A) were more frequent in refractory or early relapsing patients (10%), but had no significant impact in univariate analysis on progression‐free (PFS) or overall survival (OS). Regardless of the presence of TP53 or CDKN2A deletions, gains in 7p22 (8,5%) were associated with better PFS in univariate but not in multivariate analysis including MCL International Prognostic Index and treatment. Gains of 11q(CCDN1), suggesting gains of the CCND1/IGH fusion, were associated with worse OS and PFS in univariate and multivariate analyses. This worse prognosis impact was confirmed by FISH in an independent confirmatory cohort. This work, using a whole genome approach, confirms the broad genomic landscape of MCL and shows that gains of the CCND1/IGH fusion can be considered as a new prognostic structural variant. Genomic abnormalities of prognostic impact could be useful to strengthen or de‐escalate treatment schedules or choosing targeted therapies or CART‐cells.
ISSN:0278-0232
1099-1069
DOI:10.1002/hon.2750