PhD Scientific Days 2021
Budapest, 7-8 July 2021
PO_I_P: Pathology and Oncology I. Posters
Comprehensive Mutation Screening by Targeted Next-Generation Sequencing of Patients with Normal Karyotype Acute Myeloid Leukemia
Előadó neve
Dr. Krizsán, Szilvia
Előadó munkahelye
HCEMM-SE Molecular Oncohematology Research Group, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
Előadó telefonszáma
+36202334232
Előadó e-mail címe
krizsan.szilvia@med.semmelweis-univ.hu
Az előadás címe
Comprehensive Mutation Screening by Targeted Next-Generation Sequencing of Patients with Normal Karyotype Acute Myeloid Leukemia
Szerző(k) neve és munkahelye
Szilvia Krizsán1, Donát Alpár1*, Csaba Bödör1*
1 HCEMM-SU Molecular Oncohematology Research Group, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary
Bemutatás módja
Poszter
Szekció
Pathology and Oncology I. Posters
Language of the presentation
English
Preferred session
Pathology and Oncology
Összefoglaló szövege
Introduction: Acute myeloid leukemia (AML) is a genetically heterogeneous clonal malignancy characterized by broad spectrum of genetic alterations and a 5-year mortality rate of 75%. Conventional cytogenetics remain one of the most important prognostic factors in AML, though 40-50% of patients have normal karyotype (NK). These cases are conventionally classified as intermediate-risk, however, the clinical outcomes are highly variable.
Aim: To establish the mutational profiles of 94 AML patients with normal karyotype diagnosed in our institute between 2006 and 2019 using targeted next-generation sequencing (NGS) to detect prognostically relevant mutations according to the ELN-2017 risk classification.
Methods: Diagnostic samples were obtained from bone marrow (n=83) or peripheral blood (n=11) of patients newly diagnosed with NK AML. Median age at diagnosis was 61 years (range 26-84). Median follow up time was 11.5 months (range 0.1-121.0) with a 5-year OS of 20.5%. Targeted NGS analysis of 54 genes recurrently altered in myeloid malignancies was performed using the TruSight Myeloid Gene Panel (Illumina) with the libraries sequenced on a NextSeq500 instrument (Illumina). The allelic ratio of FLT3 ITD to wild-type FLT3 was determined by PCR and fragment analysis.
Results: NGS revealed a total of 345 somatic variants in 94 diagnostic samples with an average allelic depth of 7400x. On average, 3.7 mutations (range: 0-19) were detected per sample, with an average variant allele frequency of 33.1% (range: 5.0-96.3%), and with four patients presenting with wild-type genotype for all 54 genes analyzed. The most frequently mutated genes included NPM1 (35%), DNMT3A (31%) and FLT3 (28%) in accordance with the literature, while poor prognostic markers (ASXL1, RUNX1, TP53 mutations) were detected in 28.7% of patients. In our cohort, potentially actionable mutations were identified in 53.0% of patients. Risk classification according to ELN-2017 criteria re-assigned 57.4% of patients into a more favorable or, more commonly, a more adverse-risk group compared with the ELN-2010 criteria.
Conclusion: Targeted NGS seems to be an efficient, high-throughput assay for the genomic characterization of patients with NK AML, that enables more accurate risk assessment and identification of actionable mutations.
Funding: SGA No. 739593, EFOP-3.6.3-VEKOP-16-2017-00009, FK20_134253
University and Doctoral School
Semmelweis University, Károly Rácz Doctoral School of Clinical Medicine
Supervisor
Donát Alpár, Csaba Bödör
Publication of my abstract
I give consent to the publication of my abstract on the website of the congress.
Kind
Szabad
Status
elfogadva
Accepted presentation method
poszter
Előadás fájl jóváhagyás
nem rendelkezett róla
Előadó
4662
Start
11:52
End
11:55
Authors (legacy)
Szilvia Krizsán1, Donát Alpár1*, Csaba Bödör1*
1 HCEMM-SU Molecular Oncohematology Research Group, 1st Department of Pathology and Experimental Cancer Research, Semmelweis University, Budapest, Hungary