Application of targeted next generation sequencing for the mutational profiling of patients with acute lymphoblastic leukemia
Background: Acute lymphoblastic leukemia (ALL) is the most common cancer in children, whereas it is less common in adults. Identification of cytogenetic aberrations and a small number of molecular abnormalities are still the most important risk and therapy stratification methods in clinical practice...
| Main Authors: | , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Society of Medical Biochemists of Serbia, Belgrade
2020-01-01
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| Series: | Journal of Medical Biochemistry |
| Subjects: | |
| Online Access: | https://scindeks-clanci.ceon.rs/data/pdf/1452-8258/2020/1452-82582001072J.pdf |
| _version_ | 1818607635325255680 |
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| author | Janic Dragana Peric Jelena Karan-Djurasevic Teodora Kostic Tatjana Marjanovic Irena Stanic Bojana Pejanovic Nadja Dokmanovic Lidija Lazic Jelena Krstovski Nada Virijevic Marijana Tomin Dragica Vidovic Ana Suvajdzic-Vukovic Nada Pavlovic Sonja Tosic Natasa |
| author_facet | Janic Dragana Peric Jelena Karan-Djurasevic Teodora Kostic Tatjana Marjanovic Irena Stanic Bojana Pejanovic Nadja Dokmanovic Lidija Lazic Jelena Krstovski Nada Virijevic Marijana Tomin Dragica Vidovic Ana Suvajdzic-Vukovic Nada Pavlovic Sonja Tosic Natasa |
| author_sort | Janic Dragana |
| collection | DOAJ |
| description | Background: Acute lymphoblastic leukemia (ALL) is the most common cancer in children, whereas it is less common in adults. Identification of cytogenetic aberrations and a small number of molecular abnormalities are still the most important risk and therapy stratification methods in clinical practice today. Next generation sequencing (NGS) technology provides a large amount of data contributing to elucidation of mutational landscape of childhood (cALL) and adult ALL (aALL). Methods: We analyzed DNA samples from 34 cALL and aALL patients, using NGS targeted sequencing TruSeq Amplicon - Cancer Panel (TSACP) which targets mutational hotspots in 48 cancer related genes. Results: We identified a total of 330 variants in the coding regions, out of which only 95 were potentially protein-changing. Observed in individual patients, detected mutations predominantly disrupted Ras/RTK pathway (STK11, KIT, MET, NRAS, KRAS, PTEN). Additionally, we identified 5 patients with the same mutation in HNF1A gene, disrupting both Wnt and Notch signaling pathway. In two patients we detected variants in NOTCH1 gene. HNF1A and NOTCH1 variants were mutually exclusive, while genes involved in Ras/RTK pathway exhibit a tendency of mutation accumulation. Conclusions: Our results showed that ALL contains low number of mutations, without significant differences between cALL and aALL (median per patient 2 and 3, respectively). Detected mutations affect few key signaling pathways, primarily Ras/RTK cascade. This study contributes to knowledge of ALL mutational landscape, leading to better understanding of molecular basis of this disease. |
| first_indexed | 2024-12-16T14:29:53Z |
| format | Article |
| id | doaj.art-a2a9e05ec07a4fccb8b6c1c6e95116fa |
| institution | Directory Open Access Journal |
| issn | 1452-8258 1452-8266 |
| language | English |
| last_indexed | 2024-12-16T14:29:53Z |
| publishDate | 2020-01-01 |
| publisher | Society of Medical Biochemists of Serbia, Belgrade |
| record_format | Article |
| series | Journal of Medical Biochemistry |
| spelling | doaj.art-a2a9e05ec07a4fccb8b6c1c6e95116fa2022-12-21T22:28:16ZengSociety of Medical Biochemists of Serbia, BelgradeJournal of Medical Biochemistry1452-82581452-82662020-01-0139172821452-82582001072JApplication of targeted next generation sequencing for the mutational profiling of patients with acute lymphoblastic leukemiaJanic Dragana0Peric Jelena1Karan-Djurasevic Teodora2Kostic Tatjana3Marjanovic Irena4Stanic Bojana5Pejanovic Nadja6Dokmanovic Lidija7https://orcid.org/0000-0002-5864-4074Lazic Jelena8Krstovski Nada9Virijevic Marijana10Tomin Dragica11Vidovic Ana12Suvajdzic-Vukovic Nada13https://orcid.org/0000-0002-8807-4797Pavlovic Sonja14Tosic Natasa15https://orcid.org/0000-0002-1293-6215University of Belgrade, University Children's Hospital, Department of Hematology and Oncology, Belgrade + University of Belgrade, School of Medicine, BelgradeUniversity of Belgrade, Institute of Molecular Genetics and Genetic Engineering, Laboratory for Molecular Biomedicine, BelgradeUniversity of Belgrade, Institute of Molecular Genetics and Genetic Engineering, Laboratory for Molecular Biomedicine, BelgradeUniversity of Belgrade, Institute of Molecular Genetics and Genetic Engineering, Laboratory for Molecular Biomedicine, BelgradeUniversity of Belgrade, Institute of Molecular Genetics and Genetic Engineering, Laboratory for Molecular Biomedicine, BelgradeUniversity of Belgrade, Institute of Molecular Genetics and Genetic Engineering, Laboratory for Molecular Biomedicine, BelgradeUniversity of Belgrade, Institute of Molecular Genetics and Genetic Engineering, Laboratory for Molecular Biomedicine, BelgradeUniversity of Belgrade, University Children's Hospital, Department of Hematology and Oncology, Belgrade + University of Belgrade, School of Medicine, BelgradeUniversity of Belgrade, University Children's Hospital, Department of Hematology and Oncology, Belgrade + University of Belgrade, School of Medicine, BelgradeUniversity of Belgrade, University Children's Hospital, Department of Hematology and Oncology, Belgrade + University of Belgrade, School of Medicine, BelgradeClinical Center of Serbia, Clinic of Hematology, Belgrade + University of Belgrade, School of Medicine, BelgradeClinical Center of Serbia, Clinic of Hematology, Belgrade + University of Belgrade, School of Medicine, BelgradeClinical Center of Serbia, Clinic of Hematology, Belgrade + University of Belgrade, School of Medicine, BelgradeClinical Center of Serbia, Clinic of Hematology, Belgrade + University of Belgrade, School of Medicine, BelgradeUniversity of Belgrade, Institute of Molecular Genetics and Genetic Engineering, Laboratory for Molecular Biomedicine, BelgradeUniversity of Belgrade, Institute of Molecular Genetics and Genetic Engineering, Laboratory for Molecular Biomedicine, BelgradeBackground: Acute lymphoblastic leukemia (ALL) is the most common cancer in children, whereas it is less common in adults. Identification of cytogenetic aberrations and a small number of molecular abnormalities are still the most important risk and therapy stratification methods in clinical practice today. Next generation sequencing (NGS) technology provides a large amount of data contributing to elucidation of mutational landscape of childhood (cALL) and adult ALL (aALL). Methods: We analyzed DNA samples from 34 cALL and aALL patients, using NGS targeted sequencing TruSeq Amplicon - Cancer Panel (TSACP) which targets mutational hotspots in 48 cancer related genes. Results: We identified a total of 330 variants in the coding regions, out of which only 95 were potentially protein-changing. Observed in individual patients, detected mutations predominantly disrupted Ras/RTK pathway (STK11, KIT, MET, NRAS, KRAS, PTEN). Additionally, we identified 5 patients with the same mutation in HNF1A gene, disrupting both Wnt and Notch signaling pathway. In two patients we detected variants in NOTCH1 gene. HNF1A and NOTCH1 variants were mutually exclusive, while genes involved in Ras/RTK pathway exhibit a tendency of mutation accumulation. Conclusions: Our results showed that ALL contains low number of mutations, without significant differences between cALL and aALL (median per patient 2 and 3, respectively). Detected mutations affect few key signaling pathways, primarily Ras/RTK cascade. This study contributes to knowledge of ALL mutational landscape, leading to better understanding of molecular basis of this disease.https://scindeks-clanci.ceon.rs/data/pdf/1452-8258/2020/1452-82582001072J.pdfacute lymphoblastic leukemianext generation sequencingsomatic mutations |
| spellingShingle | Janic Dragana Peric Jelena Karan-Djurasevic Teodora Kostic Tatjana Marjanovic Irena Stanic Bojana Pejanovic Nadja Dokmanovic Lidija Lazic Jelena Krstovski Nada Virijevic Marijana Tomin Dragica Vidovic Ana Suvajdzic-Vukovic Nada Pavlovic Sonja Tosic Natasa Application of targeted next generation sequencing for the mutational profiling of patients with acute lymphoblastic leukemia Journal of Medical Biochemistry acute lymphoblastic leukemia next generation sequencing somatic mutations |
| title | Application of targeted next generation sequencing for the mutational profiling of patients with acute lymphoblastic leukemia |
| title_full | Application of targeted next generation sequencing for the mutational profiling of patients with acute lymphoblastic leukemia |
| title_fullStr | Application of targeted next generation sequencing for the mutational profiling of patients with acute lymphoblastic leukemia |
| title_full_unstemmed | Application of targeted next generation sequencing for the mutational profiling of patients with acute lymphoblastic leukemia |
| title_short | Application of targeted next generation sequencing for the mutational profiling of patients with acute lymphoblastic leukemia |
| title_sort | application of targeted next generation sequencing for the mutational profiling of patients with acute lymphoblastic leukemia |
| topic | acute lymphoblastic leukemia next generation sequencing somatic mutations |
| url | https://scindeks-clanci.ceon.rs/data/pdf/1452-8258/2020/1452-82582001072J.pdf |
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