Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

MLLT10 gene recombinations in pediatric T-Acute Lymphoblastic Leukemia

ABSTRACT: MLLT10, a 24 exons gene at 10p12, is known in leukemogenesis as partner of MLL or PICALM and recently NAP1L1. We identified HNRNPH1 and DDX3X, genes involved in RNA processing, as new MLLT10 partners in 2 cases of pediatric NOTCH1 positive T-ALL. HNRNPH1/5q35 encodes for a member of the ubiquitously expressed heterogeneous nuclear ribonucleoprotein (hnRNP) subfamily of RNA binding protein. DDX3X/Xp11.3, belongs to the big family of RNA helicases with a DEAD box domain. Whole genome analysis by SNPs and Combined Interphase FISH (CI-FISH) identified different co-operating lesions in the two cases. Fusion isoforms were found in both cases: interestingly all fusions retained the OM-LZ domain of MLLT10 that is needed to induce Acute Myeloid Leukemia in mice. Gene expression profiling (GEP) of the two new MLLT10 fusions was similar to PICALM-MLLT10 positive but differed from other HOXA positive T-ALL, suggesting MLLT10 fusions share a common leukemogenic pathway. Clinical data indicate relative good prognosis in T-ALL with MLLT10 variants. This submission represents the gene expression component of the study [For privacy reasons, SNP data will not be deposited].

ORGANISM(S): Homo sapiens

SUBMITTER: Andrea Zangrando

PROVIDER: E-GEOD-42765 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

New MLLT10 gene recombinations in pediatric T-acute lymphoblastic leukemia.

Brandimarte Lucia L Pierini Valentina V Di Giacomo Danika D Borga Chiara C Nozza Filomena F Gorello Paolo P Giordan Marco M Cazzaniga Giovanni G Te Kronnie Geertruy G Te Kronnie Geertruy G La Starza Roberta R Mecucci Cristina C

Blood 20130514 25

The MLLT10 gene, located at 10p13, is a known partner of MLL and PICALM in specific leukemic fusions generated from recurrent 11q23 and 11q14 chromosome translocations. Deep sequencing recently identified NAP1L1/12q21 as another MLLT10 partner in T-cell acute lymphoblastic leukemia (T-ALL). In pediatric T-ALL, we have identified 2 RNA processing genes, that is, HNRNPH1/5q35 and DDX3X/Xp11.3 as new MLLT10 fusion partners. Gene expression profile signatures of the HNRNPH1- and DDX3X-MLLT10 fusions ...[more]

PMID: 23673860

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Project description:Purpose: Assessment of the performance characteristics of an RNA-Seq assay designed to detect gene fusions in 573 genes to aid in the management of cancer patients. Methods: Polyadenylated RNA was converted to cDNA which was then used to prepare NGS libraries that were sequenced on a HiSeq 2500 instrument and analyzed with an in-house developed bioinformatic pipeline. Results: The assay identified 38 of 41 (93%) gene fusions previously detected by a different laboratory using FISH, RT-PCR, or RNA-Seq for a sensitivity of 93%. No false positive gene fusions were identified in 15 normal tissue specimens and 10 tumor specimens that were negative for fusions by RNA-Seq in a different laboratory (100% specificity). The assay also identified 22 fusions in 17 tumor specimens that had not been detected by other methods. Nineteen of the 22 fusions had not previously been described. Good intra- and inter-assay reproducibility was observed with complete concordance for the presence or absence of gene fusions in replicates. The analytical sensitivity of the assay was tested by diluting RNA isolated from gene fusion positive cases with fusion negative RNA. Gene fusions were generally detectable down to 12.5% dilutions for most fusions and as little as 3% for some fusions. The assay identified 38 of 41 (93%) gene fusions previously detected by a different laboratory using FISH, RT-PCR, or RNA-Seq for a sensitivity of 93%. No false positive gene fusions were identified in 15 normal tissue specimens and 10 tumor specimens that were negative for fusions by RNA-Seq in a different laboratory (100% specificity). The assay also identified 22 fusions in 17 tumor specimens that had not been detected by other methods. Nineteen of the 22 fusions had not previously been described. Good intra- and inter-assay reproducibility was observed with complete concordance for the presence or absence of gene fusions in replicates. The analytical sensitivity of the assay was tested by diluting RNA isolated from gene fusion positive cases with fusion negative RNA. Gene fusions were generally detectable down to 12.5% dilutions for most fusions and as little as 3% for some fusions. This assay should be useful for identifying cancer patients that may benefit from both FDA-approved and investigational targeted therapies.

Dataset Information

MLLT10 gene recombinations in pediatric T-Acute Lymphoblastic Leukemia

Publications

New MLLT10 gene recombinations in pediatric T-acute lymphoblastic leukemia.

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