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Chromothripsis-associated chromosome 21 amplification orchestrates transformation to blast phase MPN through targetable overexpression of DYRK1A

ABSTRACT: Chromothripsis-associated chromosome 21 amplification orchestrates transformation to blast phase MPN through targetable overexpression of DYRK1A

PROVIDER: PRJNA1236348 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR32701000_1.fastq.gz	Fastqsanger.gz
	SRR32701000_2.fastq.gz	Fastqsanger.gz
	SRR32701001_1.fastq.gz	Fastqsanger.gz
	SRR32701001_2.fastq.gz	Fastqsanger.gz
	SRR32701002_1.fastq.gz	Fastqsanger.gz

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Chromothripsis-associated chromosome 21 amplification orchestrates transformation to blast phase MPN through targetable overexpression of DYRK1A

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SNP data of MPD/MPN samples

Project description:Philadelphia-chromosome negative myeloproliferative neoplasms (MPNs) including polycythemia vera, essential thrombocythemia and primary myelofibrosis show an inherent tendency for transformation into leukemia (MPN-blast phase), which is hypothesized to be accompanied by acquisition of additional genomic lesions. We, therefore, examined chromosomal abnormalities by high-resolution single-nucleotide polymorphism (SNP) array in 88 MPN patients, as well as 71 cases with MPN-blast phase, and correlated these findings with their clinical parameters. Frequent genomic alterations were found in MPN after leukemic transformation with up to 3-fold more genomic changes per sample compared to samples in chronic phase (p<0.001). We identified commonly altered regions involved in disease progression including established targets (ETV6, TP53 and RUNX1), as well as new candidate genes on 7q, 16q, 19p and 21q. Moreover, trisomy 8 or amplification of 8q24 (MYC) was almost exclusively detected in JAK2V617F(-) cases with MPN-blast phase. Remarkably, copy-number neutral-loss of heterozygosity (CNN-LOH) on either 7q or 9p including homozygous JAK2V617F was related to decreased survival after leukemic transformation (p=0.01 and p=0.016, respectively). Our high density SNP-array analysis of MPN genomes in the chronic compared to leukemic stage identified novel target genes and provided prognostic insights associated with the evolution to leukemia. Keywords: SNP-chip To identify oncogenic lesions in MPD, we performed a genome-wide analysis of primary MPD samples using high-density SNP arrays (Affymetrix GeneChip).

2010-05-29 | E-GEOD-19647 | biostudies-arrayexpress

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