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TP53 deletion in patients with multiple myeloma and monoclonal gammopathy of undetermined significance - molecular cytogenetic analysis of 84 patients


Authors: P. Mičková 1;  J. Balcárková 1;  T. Pika 2;  V. Ščudla 2;  J. Bačovský 2;  J. Minařík 2;  K. Nevimová 1;  M. Jarošová 1
Authors‘ workplace: Hemato-onkologická klinika, LF UP a FN Olomouc 1;  III. interní klinika – NRE, LF UP a FN Olomouc 2
Published in: Transfuze Hematol. dnes,20, 2014, No. 1, p. 32-38.
Category: Comprehensive Reports, Original Papers, Case Reports

Overview

In the pathogenesis of multiple myeloma (MM), both primary and secondary genetic changes play an important role. The latter includes deletion of TP53 gene, which belongs among a group of high-risk changes associated with significantly shorter progression-free survival as well as overall survival.

Our objective was to determine the frequency and type of deletion of TP53 gene (17p13) in a group of 84 patients with MM or monoclonal gammopathy of undetermined significance (MGUS), comprising 41 males and 43 females with a median age of 61 years. In 45 patients, two distinct bone marrow samples were available, therefore we compared the results from these two collections, too. Bone marrow samples obtained from all patients were analysed using both conventional and molecular cytogenetic methods. To detect deletion of the TP53 gene, the FICTION technique with the LSI TP53/CEP 17 probe (Abbott Molecular) was used. The cut-off was set at 20%.

The analysis of 84 patients with MM revealed deletion of TP53 gene in 12 (14%) patients; one patient had chromosome 17 monosomy. Deletion of TP53 gene was not observed in any of the six individuals with MGUS. Most frequently, the deletion was observed in more advanced stages of multiple myeloma. In 10 out 12 patients, the deletion of TP53 gene was a part of a complex karyotype changes. All deletions in our cohort were monoallelic. The study also confirmed a correlation between the deletion of TP53 gene and the deletion of RB1 gene. Our results support the recommendations of the European Myeloma Network supporting the role of routine examination of MM patients for TP53 gene deletion.

Key words:
multiple myeloma, chromosomal changes, deletion of the TP53 gene, FICTION


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