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| Status |
Public on Dec 21, 2021 |
| Title |
Molecular characterization of t(2;14)(q22;q32) and t(6;14)(q25;q32) translocations in mixed myeloid/T lymphoid leukemia patients. |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
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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| Overall design |
Four patients with t(2;14)(q22;q32) and one with t(6;14)(q25;q32) translocations were compared with 14 AML patients (five NPM+/FLT3+, five NPM+/FLT3- and four PML-RARA/FLT3+).
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| Contributor(s) |
Gorello P, De Keersmaecker K, La Starza R, Kalender Atak Z, Brandimarte L, Matteucci C, Lahortiga I, Di Giacomo D, Pierini V, Gottardi E, Daraio F, Negrini M, Crescenzi B, Gianluca B, Luciano L, Ambrosetti A, Testoni N, Raspadori D, Wlodarska I, Vandenberghe P, Aerts S, Cools J, Mecucci C |
| Citation missing |
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| Submission date |
Jan 10, 2013 |
| Last update date |
Dec 21, 2021 |
| Contact name |
Zeynep Kalender Atak |
| Organization name |
KULeuven
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| Street address |
Herestraat 49
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| City |
Leuven |
| ZIP/Postal code |
3001 |
| Country |
Belgium |
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| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
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| Samples (19)
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| Relations |
| BioProject |
PRJNA186028 |
| SRA |
SRP017875 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE43417_normalized.log2.counts.txt.gz |
1.2 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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