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Identification of intragenic copy number alterations and fusion genes in paediatric high grade glioma

Carvalho, Diana Margarida Martins
Fonte: Universidade de Coimbra Publicador: Universidade de Coimbra
Tipo: Tese de Doutorado
Português
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46.26%
Os tumores cerebrais pediátricos são a segundo tumor maligno mais comum em crianças. Estes tumores são a principal causa de morte por cancro nos grupos dos 0-14 e dos 15-24 anos. Nesta tese, centramos os nossos estudos em tumores pediátricos malignos de origem glial (grau III e IV): astrocitomas, oligodendrogliomas, e glioblastomas (GBM). Apesar dos gliomas pediátricos de alto grau serem histologicamente semelhantes aos gliomas adultos malignos, estes são doenças biologicamente diferentes, possuindo perfis de número de cópias de ADN e alterações genéticas diferentes. As recentes iniciativas de sequenciação de última geração demonstraram a existência de sub-grupos de gliomas de alto grau que são caracterizados por mutações distintas: nas crianças (H3F3A K27M), nos adolescentes e jovens adultos (H3F3A G34R/V) e nos adultos de meia-idade (IDH1/2). As aberrações estruturais dos cromossomas dão origem à formação de genes de fusão que estão normalmente associados com cancro, existindo vários casos descritos em cancros de crianças e adultos. No entanto, nos gliomas pediátricos de alto grau apenas alguns genes de fusão foram descritos. Estes rearranjos estruturais normalmente dão origem a proteínas quiméricas que potencialmente podem ser importantes na resposta tumoral à terapia dirigida...

The prognostic role of intragenic copy number breakpoints and identification of novel fusion genes in paediatric high grade glioma

Carvalho, Diana; Mackay, Alan; Bjerke, Lynn; Grundy, Richard G.; Lopes, Celeste; Reis, R. M.; Jones, Chris
Fonte: BioMed Central Publicador: BioMed Central
Tipo: Artigo de Revista Científica
Publicado em //2014 Português
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56.09%
BACKGROUND: Paediatric high grade glioma (pHGG) is a distinct biological entity to histologically similar tumours arising in older adults, and has differing copy number profiles and driver genetic alterations. As functionally important intragenic copy number aberrations (iCNA) and fusion genes begin to be identified in adult HGG, the same has not yet been done in the childhood setting. We applied an iCNA algorithm to our previously published dataset of DNA copy number profiling in pHGG with a view to identify novel intragenic breakpoints. RESULTS: We report a series of 288 iCNA events in pHGG, with the presence of intragenic breakpoints itself a negative prognostic factor. We identified an increased number of iCNA in older children compared to infants, and increased iCNA in H3F3A K27M mutant tumours compared to G34R/V and wild-type. We observed numerous gene disruptions by iCNA due to both deletions and amplifications, targeting known HGG-associated genes such as RB1 and NF1, putative tumour suppressors such as FAF1 and KIDINS220, and novel candidates such as PTPRE and KCND2. We further identified two novel fusion genes in pHGG - CSGALNACT2:RET and the complex fusion DHX57:TMEM178:MAP4K3. The latter was sequence-validated and appears to be an activating event in pHGG. CONCLUSIONS: These data expand upon our understanding of the genomic events driving these tumours and represent novel targets for therapeutic intervention in these poor prognosis cancers of childhood.

Distinct leukemia phenotypes in transgenic mice and different corepressor interactions generated by promyelocytic leukemia variant fusion genes PLZF–RARα and NPM–RARα

Cheng, G.-X.; Zhu, X.-H.; Men, X.-Q.; Wang, L.; Huang, Q.-H.; Jin, X. L.; Xiong, S.-M.; Zhu, J.; Guo, W.-M.; Chen, J.-Q.; Xu, S.-F.; So, E.; Chan, L.-C.; Waxman, S.; Zelent, A.; Chen, G.-Q.; Dong, S.; Liu, J.-X.; Chen, S.-J.
Fonte: The National Academy of Sciences Publicador: The National Academy of Sciences
Tipo: Artigo de Revista Científica
Publicado em 25/05/1999 Português
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46.11%
Acute promyelocytic leukemia (APL) is characterized by a specific chromosome translocation involving RARα and one of four fusion partners: PML, PLZF, NPM, and NuMA genes. To study the leukemogenic potential of the fusion genes in vivo, we generated transgenic mice with PLZF–RARα and NPM–RARα. PLZF–RARα transgenic animals developed chronic myeloid leukemia-like phenotypes at an early stage of life (within 3 months in five of six mice), whereas three NPM–RARα transgenic mice showed a spectrum of phenotypes from typical APL to chronic myeloid leukemia relatively late in life (from 12 to 15 months). In contrast to bone marrow cells from PLZF–RARα transgenic mice, those from NPM–RARα transgenic mice could be induced to differentiate by all-trans-retinoic acid (ATRA). We also studied RARE binding properties and interactions between nuclear corepressor SMRT and various fusion proteins in response to ATRA. Dissociation of SMRT from different receptors was observed at ATRA concentrations of 0.01 μM, 0.1 μM, and 1.0 μM for RARα–RXRα, NPM–RARα, and PML–RARα, respectively, but not observed for PLZF–RARα even in the presence of 10 μM ATRA. We also determined the expression of the tissue factor gene in transgenic mice...

Fluorescence-activated sorting of totipotent embryonic stem cells expressing developmentally regulated lacZ fusion genes.

Reddy, S; Rayburn, H; von Melchner, H; Ruley, H E
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Publicado em 01/08/1992 Português
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Murine embryonic stem (ES) cells were infected with a retrovirus promoter trap vector, and clones expressing lacZ fusion genes (LacZ+) were isolated by fluorescence-activated cell sorting (FACS). Of 12 fusion genes tested, 1 was repressed when ES cells were allowed to differentiate in vitro. Two of three lacZ fusion genes tested were passed into the germ line, indicating that FACS does not significantly affect stem cell totipotency. The pattern of lacZ expression observed in vivo was consistent with that seen in vitro. Both fusion genes were expressed in preimplantation blastulas. However, a fusion gene whose expression was unaffected by in vitro differentiation was ubiquitously expressed in day-10 embryos, while the other, which showed regulated expression in vitro, was restricted to cells located along the posterior neural fold, the optic chiasm, and within the fourth ventricle. These results demonstrate the utility of using promoter trap vectors in conjunction with fluorescence sorting to disrupt developmentally regulated genes in mice.

Finding fusion genes resulting from chromosome rearrangement by analyzing the expressed sequence databases

Hahn, Yoonsoo; Bera, Tapan Kumar; Gehlhaus, Kristen; Kirsch, Ilan R.; Pastan, Ira H.; Lee, Byungkook
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
Português
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46.13%
Chromosomal rearrangements resulting in gene fusions are frequently involved in carcinogenesis. Here, we describe a semiautomatic procedure for identifying fusion gene transcripts by using publicly available mRNA and EST databases. With this procedure, we have identified 96 transcript sequences that are derived from 60 known fusion genes. Also, 47 or more additional sequences appear to be derived from 20 or more previously unknown putative fusion genes. We have experimentally verified the presence of a previously unknown IRA1/RGS17 fusion in the breast cancer cell line MCF7. The fusion gene encodes the full-length RGS17 protein, a regulator of G protein-coupled signaling, under the control of the IRA1 gene promoter. This study demonstrates that databases of ESTs can be used to discover fusion genes resulting from structural rearrangement of chromosomes.

The NPM-ALK and the ATIC-ALK Fusion Genes Can Be Detected in Non-Neoplastic Cells

Maes, Brigitte; Vanhentenrijk, Vera; Wlodarska, Iwona; Cools, Jan; Peeters, Benjamin; Marynen, Peter; De Wolf-Peeters, Christiane
Fonte: American Society for Investigative Pathology Publicador: American Society for Investigative Pathology
Tipo: Artigo de Revista Científica
Publicado em /06/2001 Português
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46.15%
Anaplastic large cell lymphoma (ALCL) is frequently associated with the t(2;5)(p23;q35) translocation. It creates a NPM-ALK fusion gene, fusing the anaplastic lymphoma kinase (ALK) gene (2p23) and the nucleophosmin (NPM) gene (5q35). Other rearrangements involving the ALK gene have recently been shown to be associated with ALCL, among which the ATIC-ALK rearrangement resulting from the inv(2)(p23q35) translocation is probably the most recurrent. The aims of the present study were to investigate the presence of NPM-ALK and ATIC-ALK fusion genes in ALCL, using a real-time 5′ exonuclease-based reverse-transcription polymerase chain reaction (RT-PCR). This sensitive technique was also applied to investigate whether both fusion genes might be detected in Hodgkin’s disease cases and in reactive lymphoid tissue. Results of the RT-PCR were compared to ALK immunostaining, cytogenetics, and fluorescence in situ hybridization (FISH) results. RT-PCR detected the NPM-ALK and ATIC-ALK fusions at high levels in 8 and 3 of a total of 13 ALK-positive ALCL cases. One ALK-positive ALCL case was negative for both fusion genes analyzed but revealed a new ALK-related translocation t(2;17)(p23;q25) by cytogenetic and FISH analysis. In addition, of the eight ALK-positive ALCL cases that were strongly positive for the NPM-ALK fusion...

Reanalysis of RNA-Sequencing Data Reveals Several Additional Fusion Genes with Multiple Isoforms

Kangaspeska, Sara; Hultsch, Susanne; Edgren, Henrik; Nicorici, Daniel; Murumägi, Astrid; Kallioniemi, Olli
Fonte: Public Library of Science Publicador: Public Library of Science
Tipo: Artigo de Revista Científica
Publicado em 31/10/2012 Português
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46.16%
RNA-sequencing and tailored bioinformatic methodologies have paved the way for identification of expressed fusion genes from the chaotic genomes of solid tumors. We have recently successfully exploited RNA-sequencing for the discovery of 24 novel fusion genes in breast cancer. Here, we demonstrate the importance of continuous optimization of the bioinformatic methodology for this purpose, and report the discovery and experimental validation of 13 additional fusion genes from the same samples. Integration of copy number profiling with the RNA-sequencing results revealed that the majority of the gene fusions were promoter-donating events that occurred at copy number transition points or involved high-level DNA-amplifications. Sequencing of genomic fusion break points confirmed that DNA-level rearrangements underlie selected fusion transcripts. Furthermore, a significant portion (>60%) of the fusion genes were alternatively spliced. This illustrates the importance of reanalyzing sequencing data as gene definitions change and bioinformatic methods improve, and highlights the previously unforeseen isoform diversity among fusion transcripts.

Fusion genes and their discovery using high throughput sequencing

Annala, M.; Parker, B.; Zhang, W.; Nykter, M.
Fonte: PubMed Publicador: PubMed
Tipo: Artigo de Revista Científica
Português
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46.23%
Fusion genes are hybrid genes that combine parts of two or more original genes. They can form as a result of chromosomal rearrangements or abnormal transcription, and have been shown to act as drivers of malignant transformation and progression in many human cancers. The biological significance of fusion genes together with their specificity to cancer cells has made them into excellent targets for molecular therapy. Fusion genes are also used as diagnostic and prognostic markers to confirm cancer diagnosis and monitor response to molecular therapies. High-throughput sequencing has enabled the systematic discovery of fusion genes in a wide variety of cancer types. In this review, we describe the history of fusion genes in cancer and the ways in which fusion genes form and affect cellular function. We also describe computational methodologies for detecting fusion genes from high-throughput sequencing experiments, and the most common sources of error that lead to false discovery of fusion genes.

RET Fusion Genes in Korean Non-Small Cell Lung Cancer

Yoo, Seung Soo; Jin, Guang; Jung, Hye Jin; Hong, Mi Jeong; Choi, Jin Eun; Jeon, Hyo-Sung; Lee, Shin Yup; Lim, Jeong Ok; Park, Jae Yong
Fonte: The Korean Academy of Medical Sciences Publicador: The Korean Academy of Medical Sciences
Tipo: Artigo de Revista Científica
Português
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46.15%
Recently, rearranged during transfection (RET) fusions have been identified in approximately 1% of non-small cell lung cancer (NSCLC). To know the prevalence of RET fusion genes in Korean NSCLCs, we examined the RET fusion genes in 156 surgically resected NSCLCs using a reverse transcriptase polymerase chain reaction. Two KIF5B-RET fusions and one CCDC6-RET fusion were identified. All three patients were females and never smokers with adenocarcinomas. RET fusion genes were mutually exclusive from EGFR, KRAS mutations and EML4-ALK fusion. RET fusion genes occur 1.9% (3 of 156) of surgically treated NSCLC patients in Koreans.

Repeated Evolution of Chimeric Fusion Genes in the β-Globin Gene Family of Laurasiatherian Mammals

Gaudry, Michael J.; Storz, Jay F.; Butts, Gary Tyler; Campbell, Kevin L.; Hoffmann, Federico G.
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
Publicado em 09/05/2014 Português
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The evolutionary fate of chimeric fusion genes may be strongly influenced by their recombinational mode of origin and the nature of functional divergence between the parental genes. In the β-globin gene family of placental mammals, the two postnatally expressed δ- and β-globin genes (HBD and HBB, respectively) have a propensity for recombinational exchange via gene conversion and unequal crossing-over. In the latter case, there are good reasons to expect differences in retention rates for the reciprocal HBB/HBD and HBD/HBB fusion genes due to thalassemia pathologies associated with the HBD/HBB “Lepore” deletion mutant in humans. Here, we report a comparative genomic analysis of the mammalian β-globin gene cluster, which revealed that chimeric HBB/HBD fusion genes originated independently in four separate lineages of laurasiatherian mammals: Eulipotyphlans (shrews, moles, and hedgehogs), carnivores, microchiropteran bats, and cetaceans. In cases where an independently derived “anti-Lepore” duplication mutant has become fixed, the parental HBD and/or HBB genes have typically been inactivated or deleted, so that the newly created HBB/HBD fusion gene is primarily responsible for synthesizing the β-type subunits of adult and fetal hemoglobin (Hb). Contrary to conventional wisdom that the HBD gene is a vestigial relict that is typically inactivated or expressed at negligible levels...

Detecting ALK, ROS1 and RET Fusion Genes in Cell Block Samples12

Zhao, Chao; Li, Xuefei; Li, Jiayu; Zhang, Yishi; Ren, Shengxiang; Chen, Xiaoxia; Zhou, Caicun
Fonte: Neoplasia Press Publicador: Neoplasia Press
Tipo: Artigo de Revista Científica
Publicado em 17/06/2014 Português
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46.23%
Whether Cell block (CB) samples are applicable to detect anaplastic lymphoma kinase (ALK), c-ros oncogene 1 (ROS1) and ret proto-oncogene (RET) fusion genes in lung adenocarcinoma is still unknown. In this study, 108 cytological samples that contained lung adenocarcinoma cells were collected, and made into CB. The CB samples all contained at least 30% lung adenocarcinoma cells. In these patients, 48 harbored EGFR mutation. Among the 50 EGFR wild type patients who detected fusion genes, 14 carried EML4-ALK fusion (28%), 2 had TPM3-ROS1 fusion (4%), and 3 harbored KIF5B-RET fusion (6%). No double fusions were found in one sample. Patients with fusion genes were younger than those without fusion genes (p = 0.032), but no significant difference was found in sex and smoking status (p > 0.05). In the thirty-five patients who received first-line chemotherapy, patients with fusion gene positive had disease control rate (DCR) (72.7% VS 50%, p > 0.05) and objective response rate (ORR) (9.1% VS 4.2%, p > 0.05) compared with those having fusion gene negative. The median progression free survival (mPFS) were 4.0 and 2.7 months in patients harbored fusion mutations and wild type, respectively (p > 0.05). We conclude that CB samples could be used to detect ALK...

The Structural Characterization of Tumor Fusion Genes and Proteins

Wang, Dandan; Li, Daixi; Qin, Guangrong; Zhang, Wen; Ouyang, Jian; Zhang, Menghuan; Xie, Lu
Fonte: Hindawi Publishing Corporation Publicador: Hindawi Publishing Corporation
Tipo: Artigo de Revista Científica
Português
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46.18%
Chromosomal translocation, which generates fusion proteins in blood tumor or solid tumor, is considered as one of the major causes leading to cancer. Recent studies suggested that the disordered fragments in a fusion protein might contribute to its carcinogenicity. Here, we investigated the sequence feature near the breakpoints in the fusion partner genes, the structure features of breakpoints in fusion proteins, and the posttranslational modification preference in the fusion proteins. Results show that the breakpoints in the fusion partner genes have both sequence preference and structural preference. At the sequence level, nucleotide combination AG is preferred before the breakpoint and GG is preferred at the breakpoint. At the structural level, the breakpoints in the fusion proteins prefer to be located in the disordered regions. Further analysis suggests the phosphorylation sites at serine, threonine, and the methylation sites at arginine are enriched in disordered regions of the fusion proteins. Using EML4-ALK as an example, we further explained how the fusion protein leads to the protein disorder and contributes to its carcinogenicity. The sequence and structural features of the fusion proteins may help the scientific community to predict novel breakpoints in fusion genes and better understand the structure and function of fusion proteins.

Patients with myeloid malignancies bearing PDGFRB fusion genes achieve durable long-term remissions with imatinib

Cheah, C.Y.; Burbury, K.; Apperley, J.F.; Huguet, F.; Pitini, V.; Gardembas, M.; Ross, D.M.; Forrest, D.; Genet, P.; Rousselot, P.; Patton, N.; Smith, G.; Dunbar, C.E.; Ito, S.; Aguiar, R.C.T.; Odenike, O.; Gimelfarb, A.; Cross, N.C.P.; Seymour, J.F.
Fonte: American Society of Hematology Publicador: American Society of Hematology
Tipo: Artigo de Revista Científica
Publicado em //2014 Português
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55.93%
Myeloid neoplasms and eosinophilia with rearrangements of PDGFRB are uncommon Philadelphia-negative myeloproliferative neoplasms. Patients are typically male, with morphologic features of a Philadelphia-negative chronic myeloproliferative syndrome or chronic myelomonocytic leukemia with eosinophilia. Reciprocal translocations involving PDGFRB result in fusion genes with constitutively activated receptor tyrosine kinase sensitive to inhibition with imatinib. We present an updated and expanded analysis of a cohort of 26 such patients treated with imatinib. After a median follow-up of 10.2 years (range, 1.8-17 years), the 10-year overall survival rate was 90% (95% confidence interval, 64%-97%); after median imatinib duration of 6.6 years (range, 0.1-12 years), the 6-year progression-free survival rate was 88% (95% confidence interval, 65%-96%). Of the patients, 96% responded; no patients who achieved a complete cytogenetic (n = 13) or molecular (n = 8) remission lost their response or progressed to blast crisis. Imatinib is well-tolerated and achieves excellent long-term responses in patients with PDGFRB rearrangements.; Chan Y. Cheah, Kate Burbury, Jane F. Apperley, Francoise Huguet, Vincenzo Pitini, Martine Gardembas, David M. Ross...

Prognostically significant fusion oncogenes in Pakistani patients with adult acute lymphoblastic leukemia and their association with disease biology and outcome

Sabir, N.; Iqbal, Z.; Aleem, A.; Awan, T.; Naeem, T.; Asad, S.; Tahir, A.H.; Absar, M.; Hasanato, R.M.W.; Basit, S.; Chishti, M.A.; Ul-Haque, M.F.; Khalid, A.M.; Sabar, M.F.; Rasool, M.; Karim, S.; Khan, M.; Samreen, B.; Akram, A.M.; Siddiqi, M.H.; et al.
Fonte: Korean Institute of Science and Technology Information Publicador: Korean Institute of Science and Technology Information
Tipo: Artigo de Revista Científica
Publicado em //2012 Português
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46.12%
Background and objectives: Chromosomal abnormalities play an important role in genesis of acute lymphoblastic leukemia (ALL) and have prognostic implications. Five major risk stratifying fusion genes in ALL are BCR-ABL, MLL-AF4, ETV6-RUNX11, E2A-PBX1 and SIL-TAL1. This work aimed to detect common chromosomal translocations and associated fusion oncogenes in adult ALL patients and study their relationship with clinical features and treatment outcome. Methods: We studied fusion oncogenes in 104 adult ALL patients using RT-PCR and interphase-FISH at diagnosis and their association with clinical characteristics and treatment outcome. Results: Five most common fusion genes i.e. BCR-ABL (t 9; 22), TCF3-PBX1 (t 1; 19), ETV6-RUNX1 (t 12; 21), MLL-AF4 (t 4; 11) and SIL-TAL1 (Del 1p32) were found in 82/104 (79%) patients. TCF3-PBX1 fusion gene was associated with lymphadenopathy, SIL-TAL1 positive patients had frequent organomegaly and usually presented with a platelets count of less than . Survival of patients with fusion gene ETV6-RUNX1 was better when compared to patients harboring other genes. MLL-AF4 and BCR-ABL positivity characterized a subset of adult ALL patients with aggressive clinical behaviour and a poor outcome. Conclusions: This is the first study from Pakistan which investigated the frequency of5 fusion oncogenes in adult ALL patients...

Characterization of fusion genes and the significantly expressed fusion isoforms in breast cancer by hybrid sequencing

Weirather, Jason L.; Afshar, Pegah Tootoonchi; Clark, Tyson A.; Tseng, Elizabeth; Powers, Linda S.; Underwood, Jason G.; Zabner, Joseph; Korlach, Jonas; Wong, Wing Hung; Au, Kin Fai
Fonte: Oxford University Press Publicador: Oxford University Press
Tipo: Artigo de Revista Científica
Português
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46.19%
We developed an innovative hybrid sequencing approach, IDP-fusion, to detect fusion genes, determine fusion sites and identify and quantify fusion isoforms. IDP-fusion is the first method to study gene fusion events by integrating Third Generation Sequencing long reads and Second Generation Sequencing short reads. We applied IDP-fusion to PacBio data and Illumina data from the MCF-7 breast cancer cells. Compared with the existing tools, IDP-fusion detects fusion genes at higher precision and a very low false positive rate. The results show that IDP-fusion will be useful for unraveling the complexity of multiple fusion splices and fusion isoforms within tumorigenesis-relevant fusion genes.

Characterization of the genomic features and expressed fusion genes in micropapillary carcinomas of the breast

Natrajan, Rachael; Wilkerson, Paul M; Marchiò, Caterina; Piscuoglio, Salvatore; Ng, Charlotte KY; Wai, Patty; Lambros, Maryou B; Samartzis, Eleftherios P; Dedes, Konstantin J; Frankum, Jessica; Bajrami, Ilirjana; Kopec, Alicja; Mackay, Alan; A'hern, Roge
Fonte: John Wiley & Sons, Ltd Publicador: John Wiley & Sons, Ltd
Tipo: Artigo de Revista Científica
Português
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46.15%
Micropapillary carcinoma (MPC) is a rare histological special type of breast cancer, characterized by an aggressive clinical behaviour and a pattern of copy number aberrations (CNAs) distinct from that of grade- and oestrogen receptor (ER)-matched invasive carcinomas of no special type (IC-NSTs). The aims of this study were to determine whether MPCs are underpinned by a recurrent fusion gene(s) or mutations in 273 genes recurrently mutated in breast cancer. Sixteen MPCs were subjected to microarray-based comparative genomic hybridization (aCGH) analysis and Sequenom OncoCarta mutation analysis. Eight and five MPCs were subjected to targeted capture and RNA sequencing, respectively. aCGH analysis confirmed our previous observations about the repertoire of CNAs of MPCs. Sequencing analysis revealed a spectrum of mutations similar to those of luminal B IC-NSTs, and recurrent mutations affecting mitogen-activated protein kinase family genes and NBPF10. RNA-sequencing analysis identified 17 high-confidence fusion genes, eight of which were validated and two of which were in-frame. No recurrent fusions were identified in an independent series of MPCs and IC-NSTs. Forced expression of in-frame fusion genes (SLC2A1–FAF1 and BCAS4–AURKA) resulted in increased viability of breast cancer cells. In addition...

Frecuencia de los genes de fusión TEL/AML1 y BCR/ABL en pacientes pediátricos con leucemia linfoblástica aguda; Frequency of TEL/AML1 and BCR/ABL fusion genes in children with acute lymphoblastic leukemia

Páez F., Eduardo; Arriagada M., Mónica; Roa S., Juan Carlos; Cabrera C., María Elena; Melo A., Angélica; Astete A., Carmen; Roa E., Iván; Artigas A., Carmen Gloria
Fonte: Universidade do Chile Publicador: Universidade do Chile
Tipo: Artículo de revista
Português
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56.18%
Background: t(12;21) (p12;q22) and t(9;22) (q34;q11) translocations have prognostic significance in acute lymphoblastic leukemia (ALL). The fusion genes TEL/AML1 y BCR/ABL, generated by these translocations, can be easily detected using molecular biology technique. Aim: To study the frequency of TEL/AML1 y BCR/ABL fusion genes in children with ALL. Material and methods: Fifity six children with ALL (age range 1 month- 14 years) were studied, thirty eight from our Temuco Hospital and 18 from the Metropolitan Region. TEL/AML1 y BCR/ABL fusion genes were detected in bone marrow samples using a reverse transcriptase nested polymerase chain reaction (RT-PCR). Results: TEL/AML 1 and BCR/ABL fusion gene transcripts were detected in 13 (23%) and 2 (4%) children, respectively. No differences in survival were observed between children with positive or negative transcripts for TEL/AML1 fusion gene. However, those positive for BCR/ABL fusion gene, had a significantly lower survival. Conclusions: The frequency of TEL/AML1 and BCR/ABL fusion gene transcripts in these children with ALL is similar to that described by other authors.; Trabajo financiado por la Universidad de La Frontera, a través del Proyecto DIUFRO #2121.

Structural analysis of the genome of breast cancer cell line ZR-75-30 identifies twelve expressed fusion genes

Schulte, Ina; Batty, Elizabeth M.; Pole, Jessica C. M.; Blood, Katherine A.; Mo, Steven; Cooke, Susanna L.; Ng, Charlotte; Howe, Kevin L.; Chin, Suet-Feung; Brenton, James D.; Caldas, Carlos; Howarth, Karen D.; Edwards, Paul A. W.
Fonte: Universidade de Cambridge Publicador: Universidade de Cambridge
Tipo: Article; Published Version
Português
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46.22%
RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are.; Abstract Background It has recently emerged that common epithelial cancers such as breast cancers have fusion genes like those in leukaemias. In a representative breast cancer cell line, ZR-75-30, we searched for fusion genes, by analysing genome rearrangements. Results We first analysed rearrangements of the ZR-75-30 genome, to around 10kb resolution, by molecular cytogenetic approaches, combining array painting and array CGH. We then compared this map with genomic junctions determined by paired-end sequencing. Most of the breakpoints found by array painting and array CGH were identified in the paired end sequencing—55% of the unamplified breakpoints and 97% of the amplified breakpoints (as these are represented by more sequence reads). From this analysis we identified 9 expressed fusion genes: APPBP2-PHF20L1...

Fusion genes in breast cancer

Batty, Elizabeth
Fonte: University of Cambridge; Department of Pathology Publicador: University of Cambridge; Department of Pathology
Tipo: Thesis; doctoral; PhD
Português
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46.26%
Fusion genes caused by chromosomal rearrangements are a common and important feature in haematological malignancies, but have until recently been seen as unimportant in epithelial cancers. The discovery of recurrent fusion genes in prostate and lung cancer suggests that fusion genes may play an important role in epithelial carcinogenesis, and that they have been previously under-reported due to the difficulties of cytogenetic analysis of solid tumours. In particular, breast cancers often have complex, highly rearranged karyotypes which have proved difficult to analyse using classical cytogenetic techniques. The aim of this project was to search for fusion genes in breast cancer by using high-resolution mapping of chromosome rearrangements in breast cancer cell lines. Mapping the chromosome rearrangements was initially done using high-resolution DNA microarrays and fluorescence in- situ hybridisation, but moved to high-throughput sequencing as it became available. Interesting candidate genes identified from the mapped chromosome rearrangements were investigated on a larger set of cell lines and primary tumours. The complete karyotypes of two breast cancer cell lines were constructed using a combination of microarrays, fluorescence microscopy...

Frecuencia de los genes de fusión TEL/AML1 y BCR/ABL en pacientes pediátricos con leucemia linfoblástica aguda

Artigas A,Carmen Gloria; Cabrera C,María Elena; Melo A,Angélica; Páez F,Eduardo; Arriagada M,Mónica; Astete A,Carmen; Roa E,Iván; Roa S,Juan Carlos
Fonte: Sociedad Médica de Santiago Publicador: Sociedad Médica de Santiago
Tipo: Artigo de Revista Científica Formato: text/html
Publicado em 01/11/2006 Português
Relevância na Pesquisa
46.16%
Background: t(12;21) (p12;q22) and t(9;22) (q34;q11) translocations have prognostic significance in acute lymphoblastic leukemia (ALL). The fusion genes TEL/AML1 y BCR/ABL, generated by these translocations, can be easily detected using molecular biology technique. Aim: To study the frequency of TEL/AML1 y BCR/ABL fusion genes in children with ALL. Material and methods: Fifity six children with ALL (age range 1 month- 14 years) were studied, thirty eight from our Temuco Hospital and 18 from the Metropolitan Region. TEL/AML1 y BCR/ABL fusion genes were detected in bone marrow samples using a reverse transcriptase nested polymerase chain reaction (RT-PCR). Results: TEL/AML 1 and BCR/ABL fusion gene transcripts were detected in 13 (23%) and 2 (4%) children, respectively. No differences in survival were observed between children with positive or negative transcripts for TEL/AML1 fusion gene. However, those positive for BCR/ABL fusion gene, had a significantly lower survival. Conclusions: The frequency of TEL/AML1 and BCR/ABL fusion gene transcripts in these children with ALL is similar to that described by other authors