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14q32 recombinations deregulating BCL11B mark a distinct Mixed Phenotype Leukemia

ABSTRACT: 14q32 recombinations deregulating BCL11B mark a distinct Mixed Phenotype Leukemia

PROVIDER: PRJNA681239 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR13160442_1.fastq.gz	Fastqsanger.gz
	SRR13160442_2.fastq.gz	Fastqsanger.gz
	SRR13160443_1.fastq.gz	Fastqsanger.gz
	SRR13160443_2.fastq.gz	Fastqsanger.gz
	SRR13160444_1.fastq.gz	Fastqsanger.gz

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14q32 recombinations deregulating BCL11B mark a distinct Mixed Phenotype Leukemia

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Project description:We characterized two recurrent translocations, i.e. t(2;14)(q22.3;q32) and t(6;14)(q25;q32), in FLT3 positive mixed myeloid/T-cell lymphoid leukemias (MLPA). Both translocations involved BCL11B at 14q32. In cases with t(2;14), the 2q22.3 breakpoint disrupted ZEB2 and produced a ZEB2-BCL11B fusion, a significant ZEB2-BCL11B over-expression with concomitant BCL11B wild type (wt) down-regulation. In cases with t(6;14), the 6q25 breakpoints fell in a 100Kb region where no genes have been mapped thus it not appeared to produce a fusion transcript. As long and short BCL11B isoforms were overexpressed in cases with t(6;14), this could be linked to loss of negative regulatory elements or juxtaposition to strong enhancers/promoters to the intact gene. As BCL11B and ZEB2-BCL11B have identical motifs for DNA and protein interactions, we hypothresized that common downstream target genes might be deregulated. Indeed, gene expression profiling analysis identified a specific signature that characterized this subgroup of MLPA and was unlike any known AML and T-ALL. Exome sequencing did no revealed common variations, thus it was used to investigate 252 candidate genes known to be involved in solid cancer or leukemias. Recurrent mutations in 13 genes, 5 of which were new somatic mutations of DNMT3A, EP300, GNAS, FAT4, and PRRX1 were identified.

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