STRN-ALK, A novel in-frame fusion with response to alectinib

AimsThe majority of pancreatic ductal adenocarcinomas (PDACs) harbour oncogenic mutations in KRAS with variants in TP53, CDKN2A and SMAD4 also prevalent. The presence of oncogenic fusions including NTRK fusions are rare but important to identify. Here we ascertain the prevalence of NTRK fusions and document their genomic characteristics in a large series of PDAC.MethodsWhole genome sequencing and RNAseq were performed on a series of patients with resected or locally advanced/metastatic PDAC collected between 2008 and 2020 at a single institution. A subset of specimens underwent immunohistochemistry (IHC) analysis. Clinical and molecular characterisation and IHC sensitivity and specificity were evaluated.Results400 patients were included (resected n=167; locally advanced/metastatic n=233). Three patients were identified as harbouring an NTRK fusion, two EML4-NTRK3 (KRAS-WT) and a single novel KANK1-NTRK3 fusion. The latter occurring in the presence of a subclonal KRAS mutation. Typical PDAC drivers were present including mutations in TP53 and CDKN2A. Substitution base signatures and tumour mutational burden were similar to typical PDAC. The prevalence of NTRK fusions was 0.8% (3/400), while in KRAS wild-type tumours, it was 6.25% (2/32). DNA prediction alone documented six false-positive cases. RNA analysis correctly identified the in-frame fusion transcripts. IHC analysis was negative in the KANK1-NTRK3 fusion but positive in a EML4-NTRK3 case, highlighting lower sensitivity of IHC.ConclusionNTRK fusions are rare; however, with emerging therapeutic options targeting these fusions, detection is vital. Reflex testing for KRAS mutations and subsequent RNA-based screening could help identify these cases in PDAC.

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Overlapping reading frames at the LYS5 locus in the yeast Yarrowia lipolytica

Molecular and Cellular Biology ◽

10.1128/mcb.10.9.4795-4806.1990 ◽

1990 ◽

Vol 10 (9) ◽

pp. 4795-4806

Author(s):

J W Xuan ◽

P Fournier ◽

N Declerck ◽

M Chasles ◽

C Gaillardin

Keyword(s):

Yarrowia Lipolytica ◽

Stop Codon ◽

Open Reading Frames ◽

Yeast Cells ◽

Lacz Gene ◽

Galactosidase Activity ◽

Phenotypic Effect ◽

Frame Fusion ◽

Beta Galactosidase ◽

Reading Frames

Mutants affected at the LYS5 locus of Yarrowia lipolytica lack detectable dehydrogenase (SDH) activity. The LYS5 gene has previously been cloned, and we present here the sequence of the 2.5-kilobase-pair (kb) DNA fragment complementing the lys5 mutation. Two large antiparallel open reading frames (ORF1 and ORF2) were observed, flanked by potential transcription signals. Both ORFs appear to be transcribed, but several lines of evidence suggest that only ORF2 is translated and encodes SDH. (i) The global amino acid compositions of Saccharomyces cerevisiae SDH and of the putative ORF2 product are similar and that of ORF1 is dissimilar. (ii) An in-frame translational fusion of ORF2 with the Escherichia coli lacZ gene was introduced into yeast cells and resulted in a beta-galactosidase activity regulated similarly to SDH; no beta-galactosidase activity was obtained with an in-frame fusion of ORF1 with lacZ. (iii) The introduction of a stop codon at the beginning of ORF2 prevented SDH expression in yeast cells, whereas no phenotypic effect was observed when ORF1 translation was blocked.

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Copy Detection Using Graphical Model

Graph-Based Methods in Computer Vision ◽

10.4018/978-1-4666-1891-6.ch014 ◽

2012 ◽

pp. 261-279

Author(s):

Shikui Wei ◽

Yao Zhao ◽

Zhenfeng Zhu

Keyword(s):

Graphical Model ◽

Graph Model ◽

Video Stream ◽

Temporal Consistency ◽

Video Content ◽

Video Copy Detection ◽

Copy Detection ◽

Video Sharing ◽

Frame Fusion ◽

Temporal Localization

With the growing popularity of video sharing websites and editing tools, it is easy for people to involve the video content from different sources into their own work, which raises the copyright problem. Content-based video copy detection attempts to track the usage of the copyright-protected video content by using video analysis techniques, which deals with not only whether a copy occurs in a query video stream but also where the copy is located and where the copy is originated from. While a lot of work has addressed the problem with good performance, less effort has been made to consider the copy detection problem in the case of a continuous query stream, for which precise temporal localization and some complex video transformations like frame insertion and video editing need to be handled. In this chapter, the authors attack the problem by employing the graphical model to facilitate the frame fusion based video copy detection approach. The key idea is to convert frame fusion problem into graph model decoding problem with the temporal consistency constraint and three relaxed constraints. This work employs the HMM model to perform frame fusion and propose a Viterbi-like algorithm to speedup frame fusion process.

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Value Frame Fusion in Cross Sector Interactions

Journal of Business Ethics ◽

10.1007/s10551-011-0785-1 ◽

2010 ◽

Vol 94 (S1) ◽

pp. 163-195 ◽

Cited By ~ 72

Author(s):

Marlene J. Le Ber ◽

Oana Branzei

Keyword(s):

Frame Fusion

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Content based video retrieval using histogram of gradients and frame fusion

Twelfth International Conference on Machine Vision (ICMV 2019) ◽

10.1117/12.2558559 ◽

2020 ◽

Author(s):

Reddy Mounika Bommisetty ◽

Ashish Khare

Keyword(s):

Video Retrieval ◽

Frame Fusion ◽

Histogram Of Gradients ◽

Content Based Video Retrieval

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Engineering of Bifunctional Enzymes with Uricase and Peroxidase Activities for Simple and Rapid Quantification of Uric Acid in Biological Samples

Catalysts ◽

10.3390/catal10040428 ◽

2020 ◽

Vol 10 (4) ◽

pp. 428

Author(s):

Thanawat Phuadraksa ◽

Jurairat Chittrakanwong ◽

Kittitouch Tullayaprayouch ◽

Naruthai Onsirisakul ◽

Sineewanlaya Wichit ◽

...

Keyword(s):

Uric Acid ◽

Low Cost ◽

Colorimetric Detection ◽

Amplex Red ◽

Bifunctional Enzymes ◽

Bifunctional Proteins ◽

Frame Fusion ◽

The Cost ◽

Optimized Conditions ◽

Catalyzed Oxidation

Serum uric acid (SUA) is an important biomarker for prognosis and management of gout and other diseases. The development of a low-cost, simple, rapid and reliable assay for SUA detection is of great importance. In the present study, to save the cost of enzyme production and to shorten the reaction time for uric acid quantification, bifunctional proteins with uricase and peroxidase activities were engineered. In-frame fusion of Candida utilis uricase (CUOX) and Vitreoscilla hemoglobin (VHb) resulted in two versions of the bifunctional protein, CUOX-VHb (CV) and VHb-CUOX (VC). To our knowledge, this is the first report to describe the production of proteins with uricase and peroxidase activities. Based on the measurement of the initial rates of the coupled reaction (between uricase and peroxidase), CV was proven to be the most efficient enzyme followed by VC and native enzymes (CUOX+VHb), respectively. CV was further applied for the development of an assay for colorimetric detection of SUA, which was based on VHb-catalyzed oxidation of Amplex Red in the presence of hydrogen peroxide (H2O2). Under the optimized conditions, the assay exhibited a linear relationship between the absorbance and UA concentration over the range of 2.5 to 50 μM, with a detection limit of 1 μM. In addition, the assay can be performed at a single pH (8.0) so adjustment of the pH for peroxidase activity was not required. This advantage helped to further reduce costs and time. The developed assay was also successfully applied to detect UA in pooled human serum with the recoveries over 94.8%. These results suggest that the proposed assay holds great potential for clinical application.

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Action Recognition Based on 3D Skeleton and RGB Frame Fusion

2019 IEEE/RSJ International Conference on Intelligent Robots and Systems (IROS) ◽

10.1109/iros40897.2019.8967570 ◽

2019 ◽

Cited By ~ 1

Author(s):

Guiyu Liu ◽

Jiuchao Qian ◽

Fei Wen ◽

Xiaoguang Zhu ◽

Rendong Ying ◽

...

Keyword(s):

Action Recognition ◽

Frame Fusion ◽

3D Skeleton

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

Journal of Clinical Oncology ◽

10.1200/jco.2013.31.15_suppl.e21523 ◽

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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