PhD Scientific Days 2022

Pathology and Oncology III. (Poster discussion will take place in the Aula during the Coffee Break)

Genomic and transcriptomic profiling of pediatric acute lymphoblastic leukemia patients in Hungary

Előadó neve

Dr. Borbála, Péterffy

Előadó munkahelye

Department of Pathology and Experimental Cancer Research

Előadó telefonszáma

+36304309791

Előadó e-mail címe

peterffy.borbala@stud.semmelweis.hu

Az előadás címe

Genomic and transcriptomic profiling of pediatric acute lymphoblastic leukemia patients in Hungary

Szerző(k) neve és munkahelye

Borbála Péterffy, Department of Pathology and Experimental Cancer Research
Szilvia Krizsán, Department of Pathology and Experimental Cancer Research

Bemutatás módja

Poszter

Szekció

Pathology and Oncology III. (Poster discussion will take place in the Aula during the Coffee Break)

Language of the presentation

English

Preferred session

Pathology and Oncology

Összefoglaló szövege

Advances in therapeutic strategies improved 5-year survival rates of patients with pediatric acute lymphoblastic leukemia (ALL), nevertheless, clinical management of relapse remains a challenge. Molecular characterization of leukemic blasts using the latest high-throughput sequencing technologies may help refine risk assessment and identify potential targets for therapeutic intervention.
In this study, we aimed at interrogating the genomic and transcriptomic landscape of Hungarian children with ALL in order to facilitate a more advanced, risk-adapted therapy selection and clinical decision-making.
Diagnostic samples of 144 B-ALL and 37 T-ALL patients were investigated. Copy number alterations (CNA) were screened with multiplex ligase-dependent probe amplification (MLPA) using SALSA MLPA P335, P327 and P383 probemixes. Somatic mutations were identified by targeted next-generation sequencing using a QIASeq Targeted DNA Custom Panel covering 102 recurrently altered, disease-relevant genes. Gene fusions were analyzed by the TruSight RNA Pan-Cancer Panel covering 1,385 genes.
CNAs were detected in 76% of B-ALL and 72% of T-ALL patients. The most frequently altered genes were CDKN2A/B (20%), PAX5 (19%) and ETV6 (18%) in B-ALL, whereas CKDN2A/B (58%), STIL (20%) and MLLT3 (20%) in T-ALL. 13% of B-ALL cases harbored IKZF1 deletion, four of which were classified in the IKZF1plus subgroup associated with very poor prognosis. Small genomic variants were most frequently observed in NRAS (21%), KRAS (19%), PTPN11 (13%) and NSD2 (10%) genes in B-ALL, NOTCH1 (58%), PHF6 (21%) and CCND3 (21%) in T-ALL. Notably, in 16% of B-ALL patients, mutations were detected in genes (FLT3, JAK2, IL7R, CRLF2) encoding actionable proteins. Gene fusions were identified in 48 % of B-ALL and 35 % of T-ALL patients, with ETV6-RUNX1, P2RY8-CRLF2, STIL-TAL1 and TCF3-PBX1 being the most frequent ones. Fusions characteristic of the BCR-ABL1-like subgroup were detected in 9% of cases with B-ALL.
NGS combined with MLPA is a fast, efficient, high-throughput method for genomic and transcriptomic profiling of children with ALL. Molecular profiling has identified actionable targets in 16% of patients, which may provide new opportunities for targeted therapeutical intervention.
Funding: FK20_134253 K21_137948 H2020-739593 EFOP-3.6.3-VEKOP-16-2017-00009 KDP-2020-1008491 TKP2021-EGA-24 TKP2021-NVA-15

University and Doctoral School

Semmelweis University, Doctoral School of Pathological Sciences

Supervisor

Dr Donát Alpár

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

6924

Start

10:45

End

10:50

Authors (legacy)

Borbála Péterffy, Department of Pathology and Experimental Cancer Research
Szilvia Krizsán, Department of Pathology and Experimental Cancer Research