scholarly journals The clinical heterogeneity of round cell sarcomas with EWSR1 / FUS gene fusions: Impact of gene fusion type on clinical features and outcome

2020 ◽  
Vol 59 (9) ◽  
pp. 525-534 ◽  
Author(s):  
Yusuke Tsuda ◽  
Lei Zhang ◽  
Paul Meyers ◽  
William D. Tap ◽  
John H. Healey ◽  
...  
Keyword(s):  
Clinical Features ◽  
Gene Fusion ◽  
Gene Fusions ◽  
Clinical Heterogeneity ◽  
Round Cell ◽  
Fusion Type

scholarly journals FOXO1 gene involvement in a non-rhabdomyosarcomatous neoplasm

2021 ◽  
Author(s):  
Simon Haefliger ◽  
Muriel Genevay ◽  
Michel Bihl ◽  
Romina Marone ◽  
Daniel Baumhoer ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Soft Tissue ◽  
Genetic Heterogeneity ◽  
Gene Fusion ◽  
Fusion Gene ◽  
Soft Tissue Tumors ◽  
Gene Fusions ◽  
Mesenchymal Tumors ◽  
Myoepithelial Differentiation ◽  
Foxo1 Gene

AbstractMyoepithelial neoplasms of soft tissue are rare tumors with clinical, morphological, immunohistochemical, and genetic heterogeneity. The morphological spectrum of these tumors is broad, and the diagnosis often requires immunostaining to confirm myoepithelial differentiation. Rarely, tumors show a morphology that is typical for myoepithelial neoplasms, while the immunophenotype fails to confirm myoepithelial differentiation. For such lesions, the term “myoepithelioma-like” tumor was introduced. Recently, two cases of myoepithelioma-like tumors of the hands and one case of the foot were described with previously never reported OGT-FOXO gene fusions. Here, we report a 50-year-old woman, with a myoepithelial-like tumor localized in the soft tissue of the forearm and carrying a OGT-FOXO1 fusion gene. Our findings extend the spectrum of mesenchymal tumors involving members of the FOXO family of transcription factors and point to the existence of a family of soft tissue tumors that carry the gene fusion of the OGT-FOXO family.

scholarly journals Undifferentiated Small Round Cell Sarcomas with Rare EWS Gene Fusions

2007 ◽  
Vol 9 (4) ◽  
pp. 498-509 ◽  
Author(s):  
Lu Wang ◽  
Rohit Bhargava ◽  
Tao Zheng ◽  
Leonard Wexler ◽  
Margaret H. Collins ◽  
...  
Keyword(s):  
Gene Fusions ◽  
Round Cell ◽  
Small Round Cell

PAX3-FKHR and PAX7-FKHR Gene Fusions Are Prognostic Indicators in Alveolar Rhabdomyosarcoma: A Report From the Children’s Oncology Group

2002 ◽  
Vol 20 (11) ◽  
pp. 2672-2679 ◽  
Author(s):  
Poul H.B. Sorensen ◽  
James C. Lynch ◽  
Stephen J. Qualman ◽  
Roberto Tirabosco ◽  
Jerian F. Lim ◽  
...  
Keyword(s):  
Clinical Outcome ◽  
Metastatic Disease ◽  
Gene Fusion ◽  
Bone Marrow Involvement ◽  
Alveolar Rhabdomyosarcoma ◽  
Outcome Analysis ◽  
Striking Difference ◽  
Gene Fusions ◽  
Fusion Transcripts ◽  
Increased Risk

PURPOSE: Alveolar rhabdomyosarcoma (ARMS) is an aggressive soft tissue malignancy of children and adolescents. Most ARMS patients express PAX3-FKHR or PAX7-FKHR gene fusions resulting from t(2;13) or t(1;13) translocations, respectively. We wished to confirm the diagnostic specificity of gene fusion detection in a large cohort of RMS patients and to evaluate whether these alterations influence clinical outcome in ARMS. PATIENTS AND METHODS: We determined PAX3-FKHR or PAX7-FKHR fusion status in 171 childhood rhabdomyosarcoma (RMS) patients entered onto the Intergroup Rhabdomyosarcoma Study IV, including 78 ARMS patients, using established reverse transcriptase polymerase chain reaction assays. All patients received central pathologic review and were treated using uniform protocols, allowing for meaningful outcome analysis. We examined the relationship between gene fusion status and clinical outcome in the ARMS cohort. RESULTS: PAX3-FKHR and PAX7-FKHR fusion transcripts were detected in 55% and 22% of ARMS patients, respectively; 23% were fusion-negative. All other RMS patients lacked transcripts, confirming the specificity of these alterations for ARMS. Fusion status was not associated with outcome differences in patients with locoregional ARMS. However, in patients presenting with metastatic disease, there was a striking difference in outcome between PAX7-FKHR and PAX3-FKHR patient groups (estimated 4-year overall survival rate of 75% for PAX7-FKHR v 8% for PAX3-FKHR; P = .0015). Multivariate analysis demonstrated a significantly increased risk of failure (P = .025) and death (P = .019) in patients with metastatic disease if their tumors expressed PAX3-FKHR. Among metastatic ARMS, bone marrow involvement was significantly higher in PAX3-FKHR–positive patients. CONCLUSION: Not only are PAX-FKHR fusion transcripts specific for ARMS, but expression of PAX3-FKHR and PAX7-FKHR identifies a very high-risk subgroup and a favorable outcome subgroup, respectively, among patients presenting with metastatic ARMS.

Reference standards for gene fusion molecular assays on cytological samples: an international validation study

2021 ◽  
pp. jclinpath-2021-207825
Author(s):  
Umberto Malapelle ◽  
Francesco Pepe ◽  
Pasquale Pisapia ◽  
Annalisa Altimari ◽  
Claudio Bellevicine ◽  
...  
Keyword(s):  
Cell Line ◽  
Validation Study ◽  
Gene Fusion ◽  
Variant Calling ◽  
Reference Standards ◽  
Gene Fusions ◽  
Wild Type ◽  
Molecular Assays ◽  
Preliminary Validation ◽  
Pap Staining

AimsGene fusions assays are key for personalised treatments of advanced human cancers. Their implementation on cytological material requires a preliminary validation that may make use of cell line slides mimicking cytological samples. In this international multi-institutional study, gene fusion reference standards were developed and validated.MethodsCell lines harbouring EML4(13)–ALK(20) and SLC34A2(4)–ROS1(32) gene fusions were adopted to prepare reference standards. Eight laboratories (five adopting amplicon-based and three hybridisation-based platforms) received, at different dilution points two sets of slides (slide A 50.0%, slide B 25.0%, slide C 12.5% and slide D wild type) stained by Papanicolaou (Pap) and May Grunwald Giemsa (MGG). Analysis was carried out on a total of 64 slides.ResultsFour (50.0%) out of eight laboratories reported results on all slides and dilution points. While 12 (37.5%) out of 32 MGG slides were inadequate, 27 (84.4%) out of 32 Pap slides produced libraries adequate for variant calling. The laboratories using hybridisation-based platforms showed the highest rate of inadequate results (13/24 slides, 54.2%). Conversely, only 10.0% (4/40 slides) of inadequate results were reported by laboratories adopting amplicon-based platforms.ConclusionsReference standards in cytological format yield better results when Pap staining and processed by amplicon-based assays. Further investigation is required to optimise these standards for MGG stained cells and for hybridisation-based approaches.

scholarly journals Spindle and Round Cell Sarcoma With EWSR1-PATZ1 Gene Fusion

2019 ◽  
Vol 43 (2) ◽  
pp. 220-228 ◽  
Author(s):  
Abhijit Chougule ◽  
Martin S. Taylor ◽  
Valentina Nardi ◽  
Ivan Chebib ◽  
Gregory M. Cote ◽  
...  
Keyword(s):  
Gene Fusion ◽  
Round Cell ◽  
Cell Sarcoma

scholarly journals DEEPrior: a deep learning tool for the prioritization of gene fusions

2020 ◽  
Vol 36 (10) ◽  
pp. 3248-3250
Author(s):  
Marta Lovino ◽  
Maria Serena Ciaburri ◽  
Gianvito Urgese ◽  
Santa Di Cataldo ◽  
Elisa Ficarra
Keyword(s):  
Deep Learning ◽  
Amino Acid ◽  
Gene Fusion ◽  
Supplementary Information ◽  
Gene Fusions ◽  
Supplementary Data ◽  
Learning Tool ◽  
Cancer Driver ◽  
Open Issue ◽  
Passenger Mutation

Abstract Summary In the last decade, increasing attention has been paid to the study of gene fusions. However, the problem of determining whether a gene fusion is a cancer driver or just a passenger mutation is still an open issue. Here we present DEEPrior, an inherently flexible deep learning tool with two modes (Inference and Retraining). Inference mode predicts the probability of a gene fusion being involved in an oncogenic process, by directly exploiting the amino acid sequence of the fused protein. Retraining mode allows to obtain a custom prediction model including new data provided by the user. Availability and implementation Both DEEPrior and the protein fusions dataset are freely available from GitHub at (https://github.com/bioinformatics-polito/DEEPrior). The tool was designed to operate in Python 3.7, with minimal additional libraries. Supplementary information Supplementary data are available at Bioinformatics online.

scholarly journals Novel BCOR-MAML3 and ZC3H7B-BCOR Gene Fusions in Undifferentiated Small Blue Round Cell Sarcomas

2016 ◽  
Vol 40 (4) ◽  
pp. 433-442 ◽  
Author(s):  
Katja Specht ◽  
Lei Zhang ◽  
Yun-Shao Sung ◽  
Marisa Nucci ◽  
Sarah Dry ◽  
...  
Keyword(s):  
Gene Fusions ◽  
Round Cell

scholarly journals Induced Chromosomal Proximity and Gene Fusions in Prostate Cancer

Science ◽  
2009 ◽  
Vol 326 (5957) ◽  
pp. 1230-1230 ◽  
Author(s):  
Ram-Shankar Mani ◽  
Scott A. Tomlins ◽  
Kaitlin Callahan ◽  
Aparna Ghosh ◽  
Mukesh K. Nyati ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Progression ◽  
Gene Fusion ◽  
Critical Role ◽  
Human Prostate ◽  
Gene Fusions ◽  
Dna Double Strand Breaks ◽  
Cell Type Specificity ◽  
Protein Coding ◽  
Subsequent Exposure

Gene fusions play a critical role in cancer progression. The mechanisms underlying their genesis and cell type specificity are not well understood. About 50% of human prostate cancers display a gene fusion involving the 5′ untranslated region of TMPRSS2, an androgen-regulated gene, and the protein-coding sequences of ERG, which encodes an erythroblast transformation–specific (ETS) transcription factor. By studying human prostate cancer cells with fluorescence in situ hybridization, we show that androgen signaling induces proximity of the TMPRSS2 and ERG genomic loci, both located on chromosome 21q22.2. Subsequent exposure of the cells to gamma irradiation, which causes DNA double-strand breaks, facilitates the formation of the TMPRSS2-ERG gene fusion. These results may help explain why TMPRSS2-ERG fusions are restricted to the prostate, which is dependent on androgen signaling.

Gene fusions evidence in a KIT/PDGFRA wild-type GIST without mutations in SDH units identified by a whole transcriptome study.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e21523-e21523
Author(s):  
Milena Urbini ◽  
Annalisa Astolfi ◽  
Valentina Indio ◽  
Maristella Saponara ◽  
Margherita Nannini ◽  
...  
Keyword(s):  
Gene Fusion ◽  
Surgical Removal ◽  
Erk Pathway ◽  
Gene Fusions ◽  
Rna Seq ◽  
Wild Type ◽  
Rna Pol Ii ◽  
Molecular Events ◽  
Frame Fusion ◽  
Whole Transcriptome

e21523 Background: A subset of KIT/PDGFRA wild-type GIST (WT) harbour mutations in SDH units. In the majority of the remaining cases of WT GIST no other molecular events are identified.We performed a RNA-seq in a WT GIST without mutations in SDH genes using next generation approach to discover molecular events in this GIST population. Methods: In 2003, a 63-year old woman underwent surgery for an ileal GIST (size 6 cm, MI 6/50HPF).After 6 years, she developed a recurrence with a single hepatic lesion. The KIT and PDGFRA analysis of the lesion did not show mutations. Therefore, she did not receive imatinib but she underwent a surgical removal. The analysis of all SDH units did not show mutations. So paired-end RNA-seq (75X2) was performed with Illumina HiScanSQ platform. After mapping the short reads on the human genome(HG19), SNVs and InDels were called by SNVMix2 with an accurate filtering procedures including predictors of mutations effect at protein level. Gene fusions discovery was done considering the agreement between DeFuse, ChimeraScan and FusionMap tools and validated by SangerSequencing using primers spanning the mRNA breakpoints. Results: Four different gene fusions and 206 non-synonymous SNVs were discovered, of which 62 were called deleterious by at least one predictor, and they are undergoing further validation. SPRED2-NELFCD gene fusion originated from an interchromosomal translocation-inversion between chr 20 and 2. The event involved exon1 of SPRED2 and exon11 of NELFCD, probably leading to inactivation of both genes. NELFCD encodes a component of the NELF complex that negatively regulates transcription elongation by RNA pol II, while SPRED2 is a member of the Sprouty /SPRED family that repress growth factor-induced activation of the MAPK/ERK pathway. The other three events were intrachromosomal aberrations: MARK2-PPFIA1 and PLA2G16-ATL3 on chr 11 and ASCC1-C10orf11 on chr 10. Only the first event led to an in-frame fusion (MARK2 ex1- PPFIA1 ex2) probably dysregulating the expression of the downstream gene. Conclusions: This is the first evidence of gene fusions in GIST. The oncogenetic role and the tumor frequency of these events deserve to be studied.

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