Concurrent TP53 and CDKN2A Gene Aberrations in Newly Diagnosed Mantle Cell Lymphoma Correlate with Chemoresistance and Call for Innovative Upfront Therapy

• Published in: Cancers Vol. 12; no. 8; p. 2120
• Main Authors: Malarikova, Diana, Berkova, Adela, Obr, Ales, Blahovcova, Petra, Svaton, Michael, Forsterova, Kristina, Kriegova, Eva, Prihodova, Eva, Pavlistova, Lenka, Petrackova, Anna, Zemanova, Zuzana, Trneny, Marek, Klener, Pavel
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 31-07-2020; MDPI
• Subjects: Ataxia telangiectasia; Ataxia telangiectasia mutated protein; B-cell lymphoma; Bone marrow; CDKN2A gene; Chemoresistance; Cyclin-dependent kinases; Cytogenetics; Enzyme inhibitors; Gene deletion; Gene expression; Genes; Genetic aspects; Genomes; Genomics; Health aspects; Hematology; Hybridization; Internal medicine; Lymphocytes B; Lymphoma; Lymphomas; Mantle cell lymphoma; Medical prognosis; Medicine; Mutation; Next-generation sequencing; p53 Protein; Patients; Stem cell transplantation; Survival analysis; Tumor suppressor genes; Variables; Czech Republic; United States > US; mantle cell lymphoma; chemoresistance; prognostic markers; CDKN2A; TP53
• ISSN: 2072-6694; 2072-6694
• DOI: 10.3390/cancers12082120

Mantle cell lymphoma (MCL) is a subtype of B-cell lymphoma with a large number of recurrent cytogenetic/molecular aberrations. Approximately 5-10% of patients do not respond to frontline immunochemotherapy. Despite many useful prognostic indexes, a reliable marker of chemoresistance is not available. We evaluated the prognostic impact of seven recurrent gene aberrations including tumor suppressor protein P53 (
) and cyclin dependent kinase inhibitor 2A (
) in the cohort of 126 newly diagnosed consecutive MCL patients with bone marrow involvement ≥5% using fluorescent in-situ hybridization (FISH) and next-generation sequencing (NGS). In contrast to
, no pathologic mutations of
were detected by NGS.
deletions were found exclusively in the context of other gene aberrations suggesting it represents a later event (after translocation t(11;14) and aberrations of
or ataxia telangiectasia mutated (
)). Concurrent deletion of
and aberration of
(deletion and/or mutation) represented the most significant predictor of short EFS (median 3 months) and OS (median 10 months). Concurrent aberration of
and
is a new, simple, and relevant index of chemoresistance in MCL. Patients with concurrent aberration of
and
should be offered innovative anti-lymphoma therapy and upfront consolidation with allogeneic stem cell transplantation.