Identification of fusion genes and characterization of transcriptome features in T-cell acute lymphoblastic leukemia
- 26 December 2017
- journal article
- research article
- Published by Proceedings of the National Academy of Sciences in Proceedings of the National Academy of Sciences of the United States of America
- Vol. 115 (2), 373-378
- https://doi.org/10.1073/pnas.1717125115
Abstract
T-cell acute lymphoblastic leukemia (T-ALL) is a clonal malignancy of immature T cells. Recently, the next-generation sequencing approach has allowed systematic identification of molecular features in pediatric T-ALL. Here, by performing RNA-sequencing and other genomewide analysis, we investigated the genomic landscape in 61 adult and 69 pediatric T-ALL cases. Thirty-six distinct gene fusion transcripts were identified, with SET-NUP214 being highly related to adult cases. Among 18 previously unknown fusions, ZBTB16-ABL1, TRA-SALL2, and involvement of NKX2-1 were recurrent events. ZBTB16-ABL1 functioned as a leukemogenic driver and responded to the effect of tyrosine kinase inhibitors. Among 48 genes with mutation rates >3%, 6 were newly found in T-ALL. An aberrantly overexpressed short mRNA transcript of the SLC17A9 gene was revealed in most cases with overexpressed TAL1, which predicted a poor prognosis in the adult group. Up-regulation of HOXA, MEF2C, and LYL1 was often present in adult cases, while TAL1 overexpression was detected mainly in the pediatric group. Although most gene fusions were mutually exclusive, they coexisted with gene mutations. These genetic abnormalities were correlated with deregulated gene expression markers in three subgroups. This study may further enrich the current knowledge of T-ALL molecular pathogenesis.Keywords
Funding Information
- Chinese National Key Basic Research Project (2013CB966800)
- Chinese Ministry of Health (201202003)
- Mega-projects of scientific research for the 12th five-year plan (2013ZX09303302)
- National Natural Science Foundation of China (81470311)
- National Natural Science Foundation of China (81670137)
- National Natural Science Foundation of China (81570122)
- National Natural Science Foundation of China (81670147)
- Natinal key research and development program (2016YFC0902800)
This publication has 38 references indexed in Scilit:
- Whole-exome sequencing in adult ETP-ALL reveals a high rate of DNMT3A mutationsBlood, 2013
- sMEK1 enhances gemcitabine anti-cancer activity through inhibition of phosphorylation of Akt/mTORApoptosis, 2012
- The genetic basis of early T-cell precursor acute lymphoblastic leukaemiaNature, 2012
- Early T-cell precursor leukaemia: a subtype of very high-risk acute lymphoblastic leukaemiaThe Lancet Oncology, 2009
- The recurrent SET-NUP214 fusion as a new HOXA activation mechanism in pediatric T-cell acute lymphoblastic leukemiaBlood, 2008
- Dynamic regulation of PU.1 expression in multipotent hematopoietic progenitorsThe Journal of Experimental Medicine, 2005
- Fusion of NUP214 to ABL1 on amplified episomes in T-cell acute lymphoblastic leukemiaNature Genetics, 2004
- Characterization of the translocation breakpoint sequences of two DEK‐CAN fusion genes present in t(6;9) acute myeloid leukemia and a SET‐CAN fusion gene found in a case of acute undifferentiated leukemiaGenes, Chromosomes and Cancer, 1992
- Coding sequences of the tal-1 gene are disrupted by chromosome translocation in human T cell leukemia.The Journal of Experimental Medicine, 1990
- Induction of Chronic Myelogenous Leukemia in Mice by the P210
bcr/abl
Gene of the Philadelphia ChromosomeScience, 1990