Analysis of BCR/ABL transcripts in healthy individuals

Boquett, Juliano André; Alves, Jesse Reis; Oliveira, Carlos Eduardo Coral de

doi:10.4238/2013.october.24.8

Cited by 23 publications

(23 citation statements)

References 20 publications

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“…collectively, these findings highlight the possibility of improving our understanding of tumor heterogeneity by selectively isolating the neoplastic exosomes. Moreover, it is known that the BCR-ABL1 transcript may also be detected in elderly healthy subjects, which may reflect the presence of a group of Ph + cells controlled by the immune system (57).…”

Section: Discussionmentioning

confidence: 99%

Feasibility of tumor‑derived exosome enrichment in the onco‑hematology leukemic model of chronic myeloid leukemia

et al. 2019

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due to the discovery of their role in intra-cellular communications, exosomes, which carry information specific to the cell of origin, have garnered considerable attention in cancer research. Moreover, there is evidence to suggest the possibility of isolating different exosome sub-populations based on target antigens at the cell surface. Philadelphia chromosome-positive (Ph +) chronic myeloid leukemia (cML) is a clonal myeloproliferative neoplasia characterized by the breakpoint cluster region-proto-oncogene 1 tyrosine-protein kinase (BcR-ABL1) fusion-gene, derived from the t (9;22) translocation. Tyrosine kinase inhibitors (TKIs) target BcR-ABL1 protein and induce major or deep molecular responses in the majority of patients. despite the fact that several studies have demonstrated the persistence of leukemic cells in the bone marrow niche, even following treatment, TKIs prolong patient survival time and facilitate treatment-free remission. These characteristics render cML a plausible model for investigating the feasibility of tumor-derived exosome fraction enrichment. In the present study, patients in the chronic phase (cP) of CML were treated with TKIs, and the quantification of the BCR-ABL1 exosomal transcript was performed using digital PcR (dPcR). The possibility of tumor-derived exosomes enrichment was confirmed, and for the first time, to the best of our knowledge, the detection of the BcR-ABL1 transcript highlighted the presence of active leukemic cells in patients with CP-CML. According to these findings, tumor-derived exosomes may be considered a novel tool for the identification of active leukemic cells, and for the assessment of innovative monitoring focused on the biological functions of exosomes in cML.

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Section: Discussionmentioning

confidence: 99%

Feasibility of tumor‑derived exosome enrichment in the onco‑hematology leukemic model of chronic myeloid leukemia

et al. 2019

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“…This is in agreement with other studies showing that chimeric RNA can be expressed in healthy individuals [37], especially when two genes involved reside closer on the genome. Moreover, even oncogenic fusion transcripts, like BCR-ABL , can be detected in normal cells [38, 39]. Knowing that, 30 healthy donors were checked for all fusion-driving rearrangements detected in SS patients in this study, but no fusion transcripts were detected.…”

Section: Resultsmentioning

confidence: 99%

Genetic rearrangements result in altered gene expression and novel fusion transcripts in Sézary syndrome

et al. 2017

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Sézary syndrome (SS) is an aggressive, leukemic cutaneous T-cell lymphoma variant. Molecular pathogenesis of SS is still unclear despite many studies on genetic alterations, gene expression and epigenetic regulations. Through whole genome and transcriptome next generation sequencing nine Sézary syndrome patients were analyzed in terms of copy number variations and rearrangements affecting gene expression. Recurrent copy number variations were detected within 8q (MYC, TOX), 17p (TP53, NCOR1), 10q (PTEN, FAS), 2p (DNMT3A), 11q (USP28), 9p (CAAP1), but no recurrent rearrangements were identified. However, expression of five genes involved in rearrangements (TMEM244, EHD1, MTMR2, RNF123 and TOX) was altered in all patients. Fifteen rearrangements detected in Sézary syndrome patients and SeAx resulted in an expression of new fusion transcripts, nine of them were in frame (EHD1-CAPN12, TMEM66-BAIAP2, MBD4-PTPRC, PTPRC-CPN2, MYB-MBNL1, TFG-GPR128, MAP4K3-FIGLA, DCP1A-CCL27, MBNL1-KIAA2018) and five resulted in ectopic expression of fragments of genes not expressed in normal T-cells (BAIAP2, CPN2, GPR128, CAPN12, FIGLA). Our results not only underscored the genomic complexity of the Sézary cancer cell genome but also showed an unpreceded large variety of novel gene rearrangements resulting in fusions transcripts and ectopically expressed genes.

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“…, oncogene expression repressed; tumor suppressor potential amplified). For example, chimeric transcripts of the well-studied chronic myeloid leukemia causing BCR - ABL (breakpoint cluster region-Abelson protooncogene) fusion gene have been detected at low levels in the blood cells of healthy individuals as well [75]. Similarly, the anti-apoptotic chimeric transcript comprised of the zinc finger genes JAZF1 (JAZF zinc finger 1) and JJAZ1 (also known as SUZ12 or SUZ12 polycomb repressive complex 2) is highly expressed in nearly 50% of all endometrial stromal sarcomas [76, 77], but has also been detected at low levels in normal endometrial stromal cells as well [24].…”

Section: Resultsmentioning

confidence: 99%

De novo assembly and characterization of breast cancer transcriptomes identifies large numbers of novel fusion-gene transcripts of potential functional significance

Mittal

McDonald

2017

BMC Med Genomics

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BackgroundGene-fusion or chimeric transcripts have been implicated in the onset and progression of a variety of cancers. Massively parallel RNA sequencing (RNA-Seq) of the cellular transcriptome is a promising approach for the identification of chimeric transcripts of potential functional significance. We report here the development and use of an integrated computational pipeline for the de novo assembly and characterization of chimeric transcripts in 55 primary breast cancer and normal tissue samples.MethodsAn integrated computational pipeline was employed to screen the transcriptome of breast cancer and control tissues for high-quality RNA-sequencing reads. Reads were de novo assembled into contigs followed by reference genome mapping. Chimeric transcripts were detected, filtered and characterized using our R-SAP algorithm. The relative abundance of reads was used to estimate levels of gene expression.Results De novo assembly allowed for the accurate detection of 1959 chimeric transcripts to nucleotide level resolution and facilitated detailed molecular characterization and quantitative analysis. A number of the chimeric transcripts are of potential functional significance including 79 novel fusion-protein transcripts and many chimeric transcripts with alterations in their un-translated leader regions. A number of chimeric transcripts in the cancer samples mapped to genomic regions devoid of any known genes. Several ‘pro-neoplastic’ fusions comprised of genes previously implicated in cancer are expressed at low levels in normal tissues but at high levels in cancer tissues.ConclusionsCollectively, our results underscore the utility of deep sequencing technologies and improved bioinformatics workflows to uncover novel and potentially significant chimeric transcripts in cancer and normal somatic tissues.Electronic supplementary materialThe online version of this article (doi:10.1186/s12920-017-0289-7) contains supplementary material, which is available to authorized users.

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Analysis of BCR/ABL transcripts in healthy individuals

Cited by 23 publications

References 20 publications

Feasibility of tumor‑derived exosome enrichment in the onco‑hematology leukemic model of chronic myeloid leukemia

Feasibility of tumor‑derived exosome enrichment in the onco‑hematology leukemic model of chronic myeloid leukemia

Genetic rearrangements result in altered gene expression and novel fusion transcripts in Sézary syndrome

De novo assembly and characterization of breast cancer transcriptomes identifies large numbers of novel fusion-gene transcripts of potential functional significance

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