TARGETED ULTRA-DEEP NGS ASSESSMENT OF TP53 MUTATIONS IN MULTIPLE MYELOMA FROM WHOLE BONE MARROW
Author(s): ,
Anna Petrackova
Affiliations:
Department of Immunology,Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc,Olomouc,Czech Republic
,
Lenka Sedlarikova
Affiliations:
Department of Immunology,Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc,Olomouc,Czech Republic
,
Jiri Minarik
Affiliations:
Department of Hemato-Oncology,Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc,Olomouc,Czech Republic
,
Michal Vasinek
Affiliations:
Department of Computer Science,Faculty of Electrical Engineering and Computer Science, Technical University of Ostrava,Ostrava,Czech Republic
,
Tereza Dyskova
Affiliations:
Department of Immunology,Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc,Olomouc,Czech Republic
,
Helena Urbankova
Affiliations:
Department of Hemato-Oncology,Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc,Olomouc,Czech Republic
,
Jaroslav Bacovsky
Affiliations:
Department of Hemato-Oncology,Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc,Olomouc,Czech Republic
,
Tomas Papajik
Affiliations:
Department of Hemato-Oncology,Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc,Olomouc,Czech Republic
Eva Kriegova
Affiliations:
Department of Immunology,Faculty of Medicine and Dentistry, Palacky University and University Hospital Olomouc,Olomouc,Czech Republic
EHA Library. PETRACKOVA A. Jun 14, 2019; 266373; PF574
Anna PETRACKOVA
Anna PETRACKOVA
Contributions
Abstract

Abstract: PF574

Type: Poster Presentation

Presentation during EHA24: On Friday, June 14, 2019 from 17:30 - 19:00

Location: Poster area

Background

Among the most important prognostic genetic aberrations in multiple myeloma (MM) are del(17p) and/or TP53 mutations. The use of the whole bone marrow (BM), when sorted MM cells are not available, may greatly simplify the NGS assessment in MM patients for clinical decisions.

Aims

Therefore, the objective of our study was to assess applicability of ultra-deep targeted NGS for analysis of TP53 mutations and other commonly mutated genes NRAS, KRAS and BRAF using the whole BM samples and compare it to results from MM sorted cells.

Methods
BM samples were obtained from MM patients (n=35, 12 M/23 F). The gDNA was isolated from whole BM (infiltration of plasma cells: median 16.4%, min-max 1.2 - 65.6%) and paired sorted MM cells. The full coding sequence and 5´and 3´UTR regions of the TP53 gene and hotspots of NRAS, KRAS and BRAF were analysed using ultra-deep NGS with the MiSeq system (Illumina). The cut-off for mutation detection was 1% variant allele frequency (VAF), the binomial distribution equation was used to determine a minimum number of mutant alleles. 

Results

Of MM patients, 22.9% (8/35) harboured mutations in TP53 gene, 20.0% (7/35) KRAS, 14.3% (5/35) NRAS and 8.6% (3/35) BRAF in the whole BM. In all patients, the VAF was in accordance with plasma cells infiltration in BM. Regarding TP53, five patients carried only TP53 mutations, two had a co-occurrence of TP53 mutations and del(17p) and one had TP53 mutation together with 17chr trisomy as assessed by FISH. In TP53, all of the mutations except one case were observed with low frequency (VAF 2-9%). In cases when paired sorted sample was available, the mutations found in the whole BM were confirmed in sorted MM cells.

Conclusion
Our results demonstrate the applicability of ultra-deep targeted NGS in assessment of TP53 mutations in the whole BM samples in MM when sorted population is not available. Moreover, our data highlights the importance of assessment of TP53 mutations in MM patients, as they may occur regardless of del(17p). Our approach may simplify the assessment of mutational landscape in MM patients and thus impacts clinical decision making.

Grant support: MZ ČR VES16-32339A, IGA UP_2019_014, MH CZ–DRO (FNOL, 00098892), NV18-03-00500

Session topic: 13. Myeloma and other monoclonal gammopathies - Biology & Translational Research

Keyword(s): Multiple myeloma, P53

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