The mutational landscape in pediatric acute lymphoblastic leukemia deciphered by whole genome sequencing
| Autor: | Carl Mårten Lindqvist, Stefan Söderhäll, Jonas Abrahamsson, Gudmar Lönnerholm, Ann-Christine Syvänen, Per Wahlberg, Rolf Larsson, Elin Övernäs, Josefine Palle, Erik Forestier, Mats Heyman, Anna Johansson, Diana Ekman, Eva C. Berglund, Amanda Raine, Johan Dahlberg, Jessica Nordlund, Behrooz Torabi Moghadam, Dan Grandér, Britt-Marie Frost, Niklas Henriksson |
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| Rok vydání: | 2014 |
| Předmět: |
Cancer genome sequencing
Male medicine.medical_specialty Kinesins acute lymphoblastic leukemia Biology medicine.disease_cause Genome Genetics medicine Humans Nerve Growth Factors Child Gene Research Articles Genetics (clinical) Exome sequencing Medicinsk genetik Whole genome sequencing Mutation whole genome sequencing Cancer och onkologi Genome Human Sequence Analysis RNA Midkine High-Throughput Nucleotide Sequencing Infant RNA sequencing Sequence Analysis DNA clonal heterogeneity Precursor Cell Lymphoblastic Leukemia-Lymphoma 3. Good health Neoplasm Proteins DNA-Binding Proteins Cancer and Oncology Child Preschool Medical genetics Human genome Female Medical Genetics |
| Zdroj: | Human Mutation |
| ISSN: | 1098-1004 |
| Popis: | Genomic characterization of pediatric acute lymphoblastic leukemia (ALL) has identified distinct patterns of genes and pathways altered in patients with well-defined genetic aberrations. To extend the spectrum of known somatic variants in ALL, we performed whole genome and transcriptome sequencing of three B-cell precursor patients, of which one carried the t(12;21)ETV6-RUNX1 translocation and two lacked a known primary genetic aberration, and one T-ALL patient. We found that each patient had a unique genome, with a combination of well-known and previously undetected genomic aberrations. By targeted sequencing in 168 patients, we identified KMT2D and KIF1B as novel putative driver genes. We also identified a putative regulatory non-coding variant that coincided with overexpression of the growth factor MDK. Our results contribute to an increased understanding of the biological mechanisms that lead to ALL and suggest that regulatory variants may be more important for cancer development than recognized to date. The heterogeneity of the genetic aberrations in ALL renders whole genome sequencing particularly well suited for analysis of somatic variants in both research and diagnostic applications. |
| Databáze: | OpenAIRE |
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