Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Neumann, M; Heesch, S; Schlee, C; Schwartz, S; Gökbuget, N; Hoelzer, D; Konstandin, NP; Ksienzyk, B; Vosberg, S; Graf, A; Krebs, S; Blum, H; Raff, T; Brüggemann, M; Hofmann, WK; Hecht, J; Bohlander, SK; Greif, PA; Baldus, CD.
Whole-exome sequencing in adult ETP-ALL reveals a high rate of DNMT3A mutations.
Blood. 2013; 121(23): 4749-4752.
Doi: 10.1182/blood-2012-11-465138
Web of Science
PubMed
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- Co-authors Med Uni Graz
- Vosberg Sebastian
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- Abstract:
- Early T-cell precursor (ETP) acute lymphoblastic leukemia (ALL) is a high-risk subgroup of T-lineage ALL characterized by specific stem cell and myeloid features. In adult ETP-ALL, no comprehensive studies on the genetic background have been performed to elucidate molecular lesions of this distinct subgroup. We performed whole-exome sequencing of 5 paired ETP-ALL samples. In addition to mutations in genes known to be involved in leukemogenesis (ETV6, NOTCH1, JAK1, and NF1), we identified novel recurrent mutations in FAT1 (25%), FAT3 (20%), DNM2 (35%), and genes associated with epigenetic regulation (MLL2, BMI1, and DNMT3A). Importantly, we verified the high rate of DNMT3A mutations (16%) in a larger cohort of adult patients with ETP-ALL (10/68). Mutations in epigenetic regulators support clinical trials, including epigenetic-orientated therapies, for this high-risk subgroup. Interestingly, more than 60% of adult patients with ETP-ALL harbor at least a single genetic lesion in DNMT3A, FLT3, or NOTCH1 that may allow use of targeted therapies.
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- Adolescent -
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- Biomarkers, Tumor - genetics
- DNA (Cytosine-5-)-Methyltransferases - genetics
- Epigenesis, Genetic -
- Exome - genetics
- Female -
- Follow-Up Studies -
- High-Throughput Nucleotide Sequencing -
- Humans -
- Male -
- Middle Aged -
- Mutation - genetics
- Precursor Cells, T-Lymphoid - pathology
- Precursor T-Cell Lymphoblastic Leukemia-Lymphoma - genetics
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- Receptor, Notch1 - genetics
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