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RET fusion

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https://www.readbyqxmd.com/read/29683817/the-etv6-ret-gene-fusion-is-found-in-etv6-rearranged-low-grade-sinonasal-adenocarcinoma-without-ntrk3-involvement
#1
Simon Andreasen, Katalin Kiss, Linea C Melchior, Jan Laco
No abstract text is available yet for this article.
April 20, 2018: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29683453/a-blood-based-test-for-the-detection-of-ros1-and-ret-fusion-transcripts-from-circulating-ribonucleic-acid-using-digital-polymerase-chain-reaction
#2
Hestia S Mellert, Kristin E Alexander, Leisa P Jackson, Gary A Pestano
We have developed novel methods for the isolation and characterization of tumor-derived circulating ribonucleic acid (cRNA) for blood-based liquid biopsy. Robust detection of cRNA recovered from blood represents a solution to a critical unmet need in clinical diagnostics. The test begins with the collection of whole blood into blood collection tubes containing preservatives that stabilize cRNA. Cell-free, exosomal, and platelet-associated RNA is isolated from plasma in this test system. The cRNA is reverse transcribed to complementary DNA (cDNA) and amplified using digital polymerase chain reaction (dPCR)...
April 5, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29667179/characteristics-of-genomic-alterations-of-lung-adenocarcinoma-in-young-never-smokers
#3
Wenxin Luo, Panwen Tian, Yue Wang, Heng Xu, Lu Chen, Chao Tang, Yang Shu, Shouyue Zhang, Zhoufeng Wang, Jun Zhang, Li Zhang, Lili Jiang, Lunxu Liu, Guowei Che, Chenglin Guo, Hong Zhang, Jiali Wang, Weimin Li
Non-small cell lung cancer (NSCLC) has been recognized as a highly heterogeneous disease with phenotypic and genotypic diversity in each subgroup. While never-smoker patients with NSCLC have been well studied through next generation sequencing, we have yet to recognize the potentially unique molecular features of young never-smoker patients with NSCLC. In this study, we conducted whole genome sequencing (WGS) to characterize the genomic alterations of 36 never-smoker Chinese patients, who were diagnosed with lung adenocarcinoma (LUAD) at 45 years or younger...
April 18, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29657135/precision-targeted-therapy-with-blu-667-for-ret-driven-cancers
#4
Vivek Subbiah, Justin F Gainor, Rami Rahal, Jason D Brubaker, Joseph L Kim, Michelle Maynard, Wei Hu, Qiongfang Cao, Michael P Sheets, Douglas Wilson, Kevin J Wilson, Lucian DiPietro, Paul Fleming, Michael Palmer, Mimi I Hu, Lori Wirth, Marcia S Brose, Sai-Hong Ignatius Ou, Matthew Taylor, Elena Garralda, Stephen Miller, Beni Wolf, Christoph Lengauer, Timothy Guzi, Erica K Evans
The receptor tyrosine kinase, rearranged during transfection (RET), is an oncogenic driver activated in multiple cancers including non-small cell lung cancer (NSCLC), medullary thyroid cancer (MTC) and papillary thyroid cancer (PTC). No approved therapies have been designed to target RET; treatment has been limited to multi-kinase inhibitors (MKIs) which can have significant off-target toxicities and limited efficacy. BLU-667 is a highly potent and selective RET inhibitor designed to overcome these limitations...
April 15, 2018: Cancer Discovery
https://www.readbyqxmd.com/read/29648570/ret-fusions-a-novel-paradigm-in-colorectal-cancer
#5
C Santos, R Sanz-Pamplona, R Salazar
No abstract text is available yet for this article.
April 10, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29617662/driver-fusions-and-their-implications-in-the-development-and-treatment-of-human-cancers
#6
Qingsong Gao, Wen-Wei Liang, Steven M Foltz, Gnanavel Mutharasu, Reyka G Jayasinghe, Song Cao, Wen-Wei Liao, Sheila M Reynolds, Matthew A Wyczalkowski, Lijun Yao, Lihua Yu, Sam Q Sun, Ken Chen, Alexander J Lazar, Ryan C Fields, Michael C Wendl, Brian A Van Tine, Ravi Vij, Feng Chen, Matti Nykter, Ilya Shmulevich, Li Ding
Gene fusions represent an important class of somatic alterations in cancer. We systematically investigated fusions in 9,624 tumors across 33 cancer types using multiple fusion calling tools. We identified a total of 25,664 fusions, with a 63% validation rate. Integration of gene expression, copy number, and fusion annotation data revealed that fusions involving oncogenes tend to exhibit increased expression, whereas fusions involving tumor suppressors have the opposite effect. For fusions involving kinases, we found 1,275 with an intact kinase domain, the proportion of which varied significantly across cancer types...
April 3, 2018: Cell Reports
https://www.readbyqxmd.com/read/29610391/application-of-genomics-to-identify-therapeutic-targets-in-recurrent-pediatric-papillary-thyroid-carcinoma
#7
Rebecca Ronsley, S Rod Rassekh, Yaoqing Shen, Anna F Lee, Colleen Jantzen, Jessica Halparin, Catherine Albert, Douglas S Hawkins, Shazhan Amed, Ralph Rothstein, Andrew J Mungall, David Dix, Geoffrey Blair, Helen Nadel, Steven J M Jones, Janessa Laskin, Marco A Marra, Rebecca J Deyell
Children with papillary thyroid carcinoma (PTC) may relapse despite response to radioactive iodine (RAI). Two children with multiply relapsed PTC underwent whole-genome and transcriptome sequencing. A TPM3-NTRK1 fusion was identified in one tumor, with outlier NTRK1 expression compared to the TCGA thyroid cancer compendium and to Illumina BodyMap normal thyroid. This patient demonstrated resolution of multiple pulmonary nodules without toxicity on oral TRK inhibitor therapy. A RET fusion was identified in the second tumor, another potentially actionable finding...
April 2018: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/29580750/targeted-next-generation-sequencing-for-reliable-detection-of-targetable-rearrangements-in-lung-adenocarcinoma-a-single-center-retrospective-study
#8
Nadezda P Velizheva, Markus P Rechsteiner, Nadejda Valtcheva, Sandra N Freiberger, Christine E Wong, Bart Vrugt, Qing Zhong, Ulrich Wagner, Holger Moch, Sven Hillinger, Isabelle Schmitt-Opitz, Alex Soltermann, Peter J Wild, Verena Tischler
Oncogenic rearrangements leading to targetable gene fusions are well-established cancer driver events in lung adenocarcinoma. Accurate and reliable detection of these gene fusions is crucial to select the appropriate targeted therapy for each patient. We compared the targeted next-generation-sequencing Oncomine Focus Assay (OFA; Thermo Fisher Scientific) with conventional ALK FISH and anti-Alk immunohistochemistry in a cohort of 52 lung adenocarcinomas (10 ALK rearranged, 18 non-ALK rearranged, and 24 untested cases)...
February 16, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29571998/identification-of-a-novel-kif13a-ret-fusion-in-lung-adenocarcinoma-by-next-generation-sequencing
#9
Xuefei Zhang, Yanlin Li, Changhong Liu, Weifeng Wang, Mo Li, Desheng Lv, Ge Sun, Hui Chen, Xiaowei Dong, Zhibo Miao, Ming Yao, Kai Wang, Hui Tian
RET fusions have been reported in 1-2% of lung adenocarcinomas, and represent an actionable target. Patients whose tumors possess RET fusion are associated with clinical benefit from the treatment with multi-kinase inhibitors such as cabozantinib and vandetanib. Further molecular screening for RET fusions is warranted. Novel KIF13A-RET fusion containing an intact RET kinase domain involving exons 1-18 of KIF13A and exons 12-20 of RET was identified in a lung cancer specimen from an 74-year-old Asian never smoker by next-generation sequencing (NGS) during clinical care...
April 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29549897/detection-of-ret-rearranged-during-transfection-variants-and-their-downstream-signal-molecules-in-ret-rearranged-lung-adenocarcinoma-patients
#10
Jeong-Oh Kim, Jung-Young Shin, Min Young Kim, Kyoung Hwa Son, Chan Kwon Jung, Tae-Jung Kim, Su Young Kim, Jae Kil Park, Sook Whan Sung, Sang Ju Bae, Hyun Jung Min, Jin-Hyoung Kang
BACKGROUND: We screened resected tumor tissues from patients with lung cancer for EGFR mutations, ALK rearrangements, and rearranged during transfection (RET) gene variants (including RET rearrangements and the Kinesin Family Member 5B (KIF5B)-RET fusion gene) using various methods including reverse transcription polymerase chain reaction (RT-PCR), transcript assays, fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). We also examined the protein expression of associated downstream signaling molecules to assess the effect of these variants on patient outcome...
March 2018: Surgical Oncology
https://www.readbyqxmd.com/read/29538669/ret-fusions-in-a-small-subset-of-advanced-colorectal-cancers-at-risk-of-being-neglected
#11
F Pietrantonio, F Di Nicolantonio, A B Schrock, J Lee, F Morano, G Fucà, P Nikolinakos, A Drilon, J F Hechtman, J Christiansen, K Gowen, G M Frampton, P Gasparini, D Rossini, C Gigliotti, S T Kim, M Prisciandaro, J Hodgson, A Zaniboni, V K Chiu, M Milione, R Patel, V Miller, A Bardelli, L Novara, L Wang, S Pupa, G Sozzi, J Ross, M Di Bartolomeo, A Bertotti, S Ali, L Trusolino, A Falcone, F de Braud, C Cremolini
Background: Recognition of rare molecular subgroups is a challenge for precision oncology and may lead to tissue-agnostic approval of targeted agents. Here we aimed to comprehensively characterize the clinical, pathological and molecular landscape of RET rearranged metastatic colorectal cancer (mCRC). Patients and methods: In this case series, we compared clinical, pathological and molecular characteristics of 24 RET rearranged mCRC patients with those of a control group of 291 patients with RET negative tumors...
March 10, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29473341/expression-and-copy-number-gains-of-the-ret-gene-in-631-early-and-mid-stage-non-small-cell-lung-cancer-cases
#12
Ling Tan, Yerong Hu, Yongguang Tao, Bin Wang, Jun Xiao, Zhenjie Tang, Ting Lu, Hao Tang
BACKGROUND: To identify whether RET is a potential target for NSCLC treatment, we examined the status of the RET gene in 631 early and mid stage NSCLC cases from south central China. METHODS: RET expression was identified by Western blot. RET-positive expression samples were verified by immunohistochemistry. RET gene mutation, copy number variation, and rearrangement were analyzed by DNA Sanger sequencing, TaqMan copy number assays, and reverse transcription-PCR...
February 23, 2018: Thoracic Cancer
https://www.readbyqxmd.com/read/29464758/a-genomic-and-clinicopathologic-study-of-non-small-cell-lung-cancers-with-discordant-ros1-gene-status-by-fluorescent-in-situ-hybridization-and-immunohistochemical-analysis
#13
Jing Zhao, Xiaotong Chen, J Zheng, M Kong, B Wang, W Ding
BACKGROUND: ROS1 immunohistochemistry (IHC) using D4D6 antibody is a useful tool for screening patients with non-small cell lung cancer (NSCLC) slated for targeted therapy. Many studies and our data have identified cases that express the ROS1 protein strongly but are negative for ROS1 by fluorescent in situ hybridization (FISH). The present study investigated the driver mutation and clinicopathologic characteristics of 26 discordant cases (ROS1 IHC-positive but FISH-negative) to find new clues for distinguishing real ROS1-rearranged cases...
February 21, 2018: Histopathology
https://www.readbyqxmd.com/read/29455670/the-rationale-for-druggability-of-ccdc6-tyrosine-kinase-fusions-in-lung-cancer
#14
REVIEW
Aniello Cerrato, Roberta Visconti, Angela Celetti
Gene fusions occur in up to 17% of solid tumours. Oncogenic kinases are often involved in such fusions. In lung cancer, almost 30% of patients carrying an activated oncogene show the fusion of a tyrosine kinase to an heterologous gene. Several genes are partner in the fusion with the three kinases ALK, ROS1 and RET in lung. The impaired function of the partner gene, in combination with the activation of the kinase, may alter the cell signaling and promote the cancer cell addiction to the oncogene. Moreover, the gene that is partner in the fusion to the kinase may affect the response to therapeutics and/or promote resistance in the cancer cells...
February 19, 2018: Molecular Cancer
https://www.readbyqxmd.com/read/29443014/recurrent-ret-gene-rearrangements-in-intraductal-carcinomas-of-salivary-gland
#15
Ilan Weinreb, Justin A Bishop, Simion I Chiosea, Raja R Seethala, Bayardo Perez-Ordonez, Lei Zhang, Yun-Shao Sung, Chun-Liang Chen, Adel Assaad, Bahram R Oliai, Cristina R Antonescu
Intraductal carcinoma (IC) is the World Health Organization designation for lesions previously called low-grade cribriform cystadenocarcinoma. The relationship of IC to salivary duct carcinoma (SDC) is controversial, but currently these are considered distinct entities. It is hypothesized that IC and SDC should have different genomic signatures that may be identifiable by next-generation sequencing. A total of 23 ICs were identified: 14 pure IC and 9 invasive carcinomas with an intraductal component. Five invasive carcinomas were subjected to next-generation paired-end RNA sequencing...
October 25, 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/29434222/a-secondary-ret-mutation-in-the-activation-loop-conferring-resistance-to-vandetanib
#16
Takashi Nakaoku, Takashi Kohno, Mitsugu Araki, Seiji Niho, Rakhee Chauhan, Phillip P Knowles, Katsuya Tsuchihara, Shingo Matsumoto, Yoko Shimada, Sachiyo Mimaki, Genichiro Ishii, Hitoshi Ichikawa, Satoru Nagatoishi, Kouhei Tsumoto, Yasushi Okuno, Kiyotaka Yoh, Neil Q McDonald, Koichi Goto
Resistance to vandetanib, a type I RET kinase inhibitor, developed in a patient with metastatic lung adenocarcinoma harboring a CCDC6-RET fusion that initially exhibited a response to treatment. The resistant tumor acquired a secondary mutation resulting in a serine-to-phenylalanine substitution at codon 904 in the activation loop of the RET kinase domain. The S904F mutation confers resistance to vandetanib by increasing the ATP affinity and autophosphorylation activity of RET kinase. A reduced interaction with the drug is also observed in vitro for the S904F mutant by thermal shift assay...
February 12, 2018: Nature Communications
https://www.readbyqxmd.com/read/29427554/sporadic-pediatric-papillary-thyroid-carcinoma-harboring-the-etv6-ntrk3-fusion-oncogene-in-a-7-year-old-japanese-girl-a-case-report-and-review-of-literature
#17
Ryota Otsubo, Zhanna Mussazhanova, Yuko Akazawa, Ayako Sato, Katsuya Matsuda, Megumi Matsumoto, Hiroshi Yano, Michiko Matsuse, Norisato Mitsutake, Takao Ando, Daisuke Niino, Takeshi Nagayasu, Masahiro Nakashima
BACKGROUND: There have been great concerns about pediatric thyroid cancers after the accident at the Fukushima Daiichi Nuclear Power Plant in 2011. CASE PRESENTATION: We report a case of a 7-year-old Japanese girl with sporadic papillary thyroid carcinoma (PTC) harboring an ETV6/NTRK3 rearrangement. The patient presented with tumors in both lobes and underwent thyroidectomy followed by radioactive iodine (RAI) ablation. Histopathology showed a classic type of PTC with cervical lymph node metastasis...
February 10, 2018: Journal of Pediatric Endocrinology & Metabolism: JPEM
https://www.readbyqxmd.com/read/29372843/analysis-of-fusion-genes-by-nanostring-system-a-role-in-lung-cytology
#18
Greta Alì, Rossella Bruno, Mauro Savino, Riccardo Giannini, Serena Pelliccioni, Maura Menghi, Laura Boldrini, Agnese Proietti, Antonio Chella, Alessandro Ribechini, Gabriella Fontanini
CONTEXT: - Patients with non-small cell lung cancer harboring ALK receptor tyrosine kinase ( ALK), ROS proto-oncogene 1 ( ROS1), and ret proto-oncogene ( RET) gene rearrangements can benefit from specific kinase inhibitors. Detection of fusion genes is critical for determining the best treatment. Assessing rearrangements in non-small cell lung cancer remains challenging, particularly for lung cytology. OBJECTIVE: - To examine the possible application of the multiplex, transcript-based NanoString system (NanoString Technologies, Seattle, Washington) in the evaluation of fusion genes in lung adenocarcinoma samples...
April 2018: Archives of Pathology & Laboratory Medicine
https://www.readbyqxmd.com/read/29345728/analytical-performance-of-the-thyroseq-v3-genomic-classifier-for-cancer-diagnosis-in-thyroid-nodules
#19
Marina N Nikiforova, Stephanie Mercurio, Abigail I Wald, Michelle Barbi de Moura, Keith Callenberg, Lucas Santana-Santos, William E Gooding, Linwah Yip, Robert L Ferris, Yuri E Nikiforov
BACKGROUND: Molecular tests have clinical utility for thyroid nodules with indeterminate fine-needle aspiration (FNA) cytology, although their performance requires further improvement. This study evaluated the analytical performance of the newly created ThyroSeq v3 test. METHODS: ThyroSeq v3 is a DNA- and RNA-based next-generation sequencing assay that analyzes 112 genes for a variety of genetic alterations, including point mutations, insertions/deletions, gene fusions, copy number alterations, and abnormal gene expression, and it uses a genomic classifier (GC) to separate malignant lesions from benign lesions...
January 18, 2018: Cancer
https://www.readbyqxmd.com/read/29326158/reciprocal-spatiotemporally-controlled-apoptosis-regulates-wolffian-duct-cloaca-fusion
#20
Masato Hoshi, Antoine Reginensi, Matthew S Joens, James A J Fitzpatrick, Helen McNeill, Sanjay Jain
The epithelial Wolffian duct (WD) inserts into the cloaca (primitive bladder) before metanephric kidney development, thereby establishing the initial plumbing for eventual joining of the ureters and bladder. Defects in this process cause common anomalies in the spectrum of congenital anomalies of the kidney and urinary tract (CAKUT). However, developmental, cellular, and molecular mechanisms of WD-cloaca fusion are poorly understood. Through systematic analysis of early WD tip development in mice, we discovered that a novel process of spatiotemporally regulated apoptosis in WD and cloaca was necessary for WD-cloaca fusion...
March 2018: Journal of the American Society of Nephrology: JASN
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