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https://www.readbyqxmd.com/read/28932588/kras-mutation-positive-mucinous-adenocarcinoma-originating-in-the-thymus
#1
Ichiro Sakanoue, Hiroshi Hamakawa, Daichi Fujimoto, Yukihiro Imai, Kazuhiro Minami, Keisuke Tomii, Yutaka Takahashi
Thymic carcinoma is a rare, aggressive disease with a low 5-year survival rate. The most common histological neoplastic thymic tumor subtype is squamous cell. We describe an interesting case of a 39-year-old woman who presented with mucinous adenocarcinoma that originated in the thymus and was treated via radical resection and venoplasty of the superior vena cava (SVC). Macroscopically, the resected tumor contained a solid region and multiple cysts with abundant mucin. Microscopic examination showed a papillary growth pattern of goblet cells with round nuclei...
August 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28931104/-molecular-diagnostics-of-alk-positive-lung-cancer
#2
József Tímár, Gábor Lotz, Erzsébet Rásó, Judit Moldvay
ALK translocation is the 3rd most frequent genetic aberration in lung adenocarcinoma, and several inhibitors are now clinically available in first and second line settings. Accordingly, molecular diagnostics of ALK-positive lung cancer is very important and can be done with the rational combination of several methods. All international recommendations suggest that, except for cytological samples, screening technology for ALK-positive tumors is immunohistochemistry using a validated test. It is highly recommended that in case of ALK protein positive samples gene translocation must be confirmed by fluorescent in situ hybridization (FISH)...
September 20, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28915622/genomic-analysis-integrated-whole-exome-sequencing-of-neuroblastomas-identifies-genetic-mutations-in-axon-guidance-pathway
#3
Yuanyuan Li, Miki Ohira, Yong Zhou, Teng Xiong, Wen Luo, Chao Yang, Xiangchun Li, Zhibo Gao, Rui Zhou, Yohko Nakamura, Takehiko Kamijo, Yasuhiko Kaneko, Takeshi Taketani, Junichi Ueyama, Tatsuro Tajiri, Hongyan Zhang, Jian Wang, Huanming Yang, Ye Yin, Akira Nakagawara
Neuroblastoma (NB) is a childhood solid malignant tumor originating from precursor cells of the peripheral nervous system. We have previously established a risk classification system based on DNA copy number profiles. To further explore the pathogenesis of NBs in distinct risk groups, we performed whole-exome sequencing analysis of 57 primary and 7 recurrent/metastatic tumors with unique chromosomal aberration profiles as categorized by our genomic sub-grouping system. Overall, a low frequency of somatic mutations was found...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915608/a-genome-wide-microrna-profiling-indicates-mir-424-5p-and-mir-503-5p-as-regulators-of-alk-expression-in-neuroblastoma
#4
Marilena De Mariano, Sara Stigliani, Stefano Moretti, Federica Parodi, Michela Croce, Cinzia Bernardi, Aldo Pagano, Gian Paolo Tonini, Silvano Ferrini, Luca Longo
The discovery of missense mutations of ALK gene identified this receptor tyrosine kinase as a therapeutic target in neuroblastoma (NB). Moreover, a high level of ALK protein has been associated with metastatic NB cases and with a worse prognosis, suggesting that also ALK overexpression is involved in NB tumorigenesis. Since miRNAs play key roles in the regulation of gene expression we aimed at identifying those miRNAs that can regulate ALK in NB. We therefore analyzed the genome-wide expression profile of miRNAs in two sample sets of 16 NB cell lines and 22 NB samples by using miRNA microarrays...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28914263/coexistent-genetic-alterations-involving-alk-ret-ros1-or-met-in-15-cases-of-lung-adenocarcinoma
#5
Zhenya Tang, Jianjun Zhang, Xinyan Lu, Wei Wang, Hui Chen, Melissa K Robinson, Joanne Cheng, Guilin Tang, L Jeffrey Medeiros
In lung cancer, targetable activating alterations in cancer genes, such as EGFR, ALK, RET, ROS1 and MET, are usually mutually exclusive. Rare lung cancer cases with coexistent alterations of EGFR and ALK or EGFR mutations with RET or ROS1 rearrangements have been reported. In this study, we report 15 patients (3 men and 12 women; 14 Caucasians and 1 African American) with ages ranging from 43 to 81 years (median 60 years) with lung adenocarcinoma in which coexistent alterations of two cancer-associated genes, including ALK, ROS1, or RET rearrangement or MET amplification were present...
September 15, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28912153/comprehensive-genomic-profiling-of-282-pediatric-low-and-high-grade-gliomas-reveals-genomic-drivers-tumor-mutational-burden-and-hypermutation-signatures
#6
Adrienne Johnson, Eric Severson, Laurie Gay, Jo-Anne Vergilio, Julia Elvin, James Suh, Sugganth Daniel, Mandy Covert, Garrett M Frampton, Sigmund Hsu, Glenn J Lesser, Kimberly Stogner-Underwood, Ryan T Mott, Sarah Z Rush, Jennifer J Stanke, Sonika Dahiya, James Sun, Prasanth Reddy, Zachary R Chalmers, Rachel Erlich, Yakov Chudnovsky, David Fabrizio, Alexa B Schrock, Siraj Ali, Vincent Miller, Philip J Stephens, Jeffrey Ross, John R Crawford, Shakti H Ramkissoon
BACKGROUND: Pediatric brain tumors are the leading cause of death for children with cancer in the U.S. Incorporating next-generation sequencing data for both pediatric low-grade (pLGGs) and high-grade gliomas (pHGGs) can inform diagnostic, prognostic, and therapeutic decision-making. MATERIALS AND METHODS: We performed comprehensive genomic profiling on 282 pediatric gliomas (157 pHGGs, 125 pLGGs), sequencing 315 cancer-related genes and calculating the tumor mutational burden (TMB; mutations per megabase [Mb])...
September 14, 2017: Oncologist
https://www.readbyqxmd.com/read/28903424/identification-and-characterization-of-a-novel-scyl3-ntrk1-rearrangement-in-a-colorectal-cancer-patient
#7
Massimo Milione, Elena Ardini, Jason Christiansen, Emanuele Valtorta, Silvio Veronese, Roberta Bosotti, Alessio Pellegrinelli, Adele Testi, Filippo Pietrantonio, Giovanni Fucà, Ge Wei, Danielle Murphy, Salvatore Siena, Antonella Isacchi, Filippo De Braud
In colorectal cancer patients, chromosomal rearrangements involving NTRK1 gene (encoding the TRKA protein) are shown in a small subset of patients and are associated with the constitutive activation of the kinase domain of TRKA. In turn, activated TRKA-fusion proteins are associated with proliferation and survival in colorectal cancer tumors. Here we report the identification and functional characterization of a new SCYL3-NTRK1 fusion gene in a 61-year-old colorectal cancer patient. To our knowledge, this fusion protein has never been previously documented in oncological patients...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28887531/homogeneity-and-high-concordance-of-alk-translocation-in-primary-lung-adenocarcinoma-and-paired-lymph-node-metastasis
#8
Wei Ma, Lei Guo, Ling Shan, Xiuyun Liu, Ning Lyu, Jianming Ying
Translocation of anaplastic lymphoma kinase (ALK) gene is an important determinator for the response to ALK tyrosine kinase inhibitor (TKI) in non-small-cell lung cancer (NSCLC) patients. The existence of genetic heterogeneity will affect the results of molecular testing, especially in biopsy samples from primary or metastatic sites of patients with advanced stage NSCLC. We intended to explore the heterogeneity of ALK gene translocation in excision specimens and to examine the existence of discordance of ALK status between primary tumours and corresponding lymph node metastases...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28882182/-s-crizotinib-induces-apoptosis-in-human-non-small-cell-lung-cancer-cells-by-activating-ros-independent-of-mth1
#9
Xuanxuan Dai, Guilong Guo, Peng Zou, Ri Cui, Weiqian Chen, Xi Chen, Changtian Yin, Wei He, Rajamanickam Vinothkumar, Fan Yang, Xiaohua Zhang, Guang Liang
BACKGROUND: Non-small cell lung cancer (NSCLC) accounts for approximately 80-85% of all lung cancers and is usually diagnosed at an advanced stage with poor prognosis. Targeted therapy has produced unprecedented outcomes in patients with NSCLC as a number of oncogenic drivers have been found. Crizotinib, a selective small-molecule inhibitor, has been widely used for the treatment of NSCLC patients with ALK gene rearrangements. A recent study has also shown that (S)-enantiomer of crizotinib exhibits anticancer activity by targeting the protein mutT homologue (MTH1)...
September 7, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28881856/strategies-targeting-angiogenesis-in-advanced-non-small-cell-lung-cancer
#10
REVIEW
Jun Wang, Jianpeng Chen, Yan Guo, Baocheng Wang, Huili Chu
Tumor angiogenesis is a frequent event in the development and progression of non-small cell lung cancer (NSCLC) and has been identified as a promising therapeutic target. The vascular endothelial growth factor (VEGF) family and other angiogenic factors, including fibroblast growth factor and platelet-derived growth factor, promote the growth of newly formed vessels from preexisting vessels and change the tumor microenvironment. To date, two antiangiogenic monoclonal antibodies, bevacizumab and ramucirumab, which target VEGF-A and its receptor VEGF receptor-2, respectively, have been approved for the treatment of locally advanced or metastatic NSCLC when added to first-line standard chemotherapy...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28871274/paired-expression-analysis-of-tumor-cell-surface-antigens
#11
Rimas J Orentas, Sivasish Sindiri, Christine Duris, Xinyu Wen, Jianbin He, Jun S Wei, Jason Jarzembowski, Javed Khan
Adoptive immunotherapy with antibody-based therapy or with T cells transduced to express chimeric antigen receptors (CARs) is useful to the extent that the cell surface membrane protein being targeted is not expressed on normal tissues. The most successful CAR-based (anti-CD19) or antibody-based therapy (anti-CD20) in hematologic malignancies has the side effect of eliminating the normal B cell compartment. Targeting solid tumors may not provide a similar expendable marker. Beyond antibody to Her2/NEU and EGFR, very few antibody-based and no CAR-based therapies have seen broad clinical application for solid tumors...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28864950/correlation-of-early-pet-findings-with-tumor-response-to-molecular-targeted-agents-in-patients-with-advanced-driver-mutated-non-small-cell-lung-cancer
#12
Tomonobu Koizumi, Toshirou Fukushima, Daisuke Gomi, Takashi Kobayashi, Nodoka Sekiguchi, Keiko Mamiya, Kazunari Tateishi, Akane Katou, Kazuhiro Oguchi
Recent advances in positron emission tomography with fluorine-18-fluorodeoxyglucose (FDG-PET) have facilitated not only the diagnosis and staging of lung cancer, but also the prediction of treatment outcome. The present study was designed to assess the usefulness of early FDG-PET examination for predicting subsequent tumor size reduction in response to molecular targeted agents in metastatic non-small cell lung cancer (NSCLC) with sensitive gene anomalies. I. In 29 targeted lesions of 10 NSCLC patients, changes in FDG uptake before and on day 7 after the initiation of molecular targeted therapy (gefitinib, n = 7; crizotinib, n = 3) were compared with subsequent radiographic tumor size reduction by RECIST...
September 1, 2017: Medical Oncology
https://www.readbyqxmd.com/read/28857077/fusions-in-solid-tumours-diagnostic-strategies-targeted-therapy-and-acquired-resistance
#13
REVIEW
Alison M Schram, Matthew T Chang, Philip Jonsson, Alexander Drilon
Structural gene rearrangements resulting in gene fusions are frequent events in solid tumours. The identification of certain activating fusions can aid in the diagnosis and effective treatment of patients with tumours harbouring these alterations. Advances in the techniques used to identify fusions have enabled physicians to detect these alterations in the clinic. Targeted therapies directed at constitutively activated oncogenic tyrosine kinases have proven remarkably effective against cancers with fusions involving ALK, ROS1, or PDGFB, and the efficacy of this approach continues to be explored in malignancies with RET, NTRK1/2/3, FGFR1/2/3, and BRAF/CRAF fusions...
August 31, 2017: Nature Reviews. Clinical Oncology
https://www.readbyqxmd.com/read/28845578/patient-harboring-a-novel-pik3ca-point-mutation-after-acquired-resistance-to-crizotinib-in-an-adenocarcinoma-with-ros1-rearrangement-a-case-report-and-literature-review
#14
Chun-Wei Xu, Wen-Xian Wang, Rong-Fang Huang, Cheng He, Xing-Hui Liao, You-Cai Zhu, Kai-Qi Du, Wu Zhuang, Yan-Ping Chen, Gang Chen, Mei-Yu Fang
ROS1 rearrangement occurs in 1-2% of non-small cell lung cancer (NSCLC) cases. These patients would benefit from treatment with the anaplastic lymphoma kinase inhibitor, crizotinib; however, resistance to crizotinib inevitably develops in such patients despite an initial response. The mechanism of acquired resistance to crizotinib in patients with NSCLC with ROS1 rearrangement has not yet been identified. Herein, we report a case of a 66-year-old woman diagnosed with adenocarcinoma. PCR revealed no EGFR or ALK mutations...
August 28, 2017: Thoracic Cancer
https://www.readbyqxmd.com/read/28843992/tracking-met-de-addiction-in-lung-cancer-a-road-towards-the-oncogenic-target
#15
REVIEW
S Pilotto, L Carbognin, N Karachaliou, P C Ma, R Rosell, G Tortora, E Bria
The discovery of druggable oncogenic drivers (i.e. EGFR and ALK), along with the introduction of comprehensive tumor genotyping techniques into the daily clinical practice define non-small-cell lung cancer (NSCLC) asa group of heterogeneous diseases, requiring a context-personalized clinico-therapeutical approach. Among the most investigated biomarkers, the MET proto-oncogene has been extensively demonstrated to play a crucial role throughout the lung oncogenesis, unbalancing the proliferation/apoptosis signaling and influencing the epithelial-mesenchymal transition and the invasive phenotype...
August 20, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28843522/an-analysis-of-the-gene-interaction-networks-identifying-the-role-of-parp1-in-metastasis-of-non-small-cell-lung-cancer
#16
Kai Chen, Yajie Li, Hui Xu, Chunfeng Zhang, Zhiqiang Li, Wei Wang, Baofeng Wang
Though there were many researches about the effects of cancer cells on non-small cell lung cancer currently, it has been rarely reported completed oncogene and its mechanism in tumors by far. Here, we used biological methods with known oncogene of NSCLC to find new oncogene and explore its functionary mechanism in NSCLC. The study firstly built NSCLC genetic interaction network based on bioinformatics methods and then together with shortest path algorithm and significance test confirmed core genes were closely involved with given genes; real-time qPCR was conducted to detect expression levels between patients with NSCLC and normal people; additionally, detection of PARP1's role in migration and invasion was performed by Transwell assays and wound-healing...
August 23, 2017: Gene
https://www.readbyqxmd.com/read/28840016/lung-adenocarcinoma-from-molecular-basis-to-genome-guided-therapy-and-immunotherapy
#17
REVIEW
Roberto Chalela, Víctor Curull, César Enríquez, Lara Pijuan, Beatriz Bellosillo, Joaquim Gea
Although adenocarcinoma (ADC) is the most frequent lung cancer, its diagnosis is often late, when the local invasion is important and/or the metastases have already appeared. Therefore, the mortality at 5 years is still very high, ranging from 51% to 99%, depending on the stage. The implementation of different molecular techniques has allowed genomic studies even in relatively small histological samples such as obtained with non-invasive or minimally invasive techniques, facilitating a better phenotyping of lung ADC...
July 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28838404/validation-of-alk-ros1-dual-break-apart-fish-probe-probe-in-non-small-cell-lung-cancer
#18
Sun Min Lim, Hyun Chang, Yoon Jin Cha, Shile Liang, Yan Chin Tai, Gu Li, Ekaterina Pestova, Frank Policht, Thomas Perez, Ross A Soo, Won Young Park, Hye Ryun Kim, Hyo Sup Shim, Byoung Chul Cho
BACKGROUND: ALK and ROS1 gene rearrangements are distinct molecular subsets of non-small-cell lung cancer (NSCLC), and they are strong predictive biomarkers of response to ALK/ROS1 inhibitors, such as crizotinib. Thus, it is clinically important to develop an effective screening strategy to detect patients who will benefit from such treatment. In this study, we aimed to validate analytical performance of Vysis ALK/ROS1 Dual Break Apart Probe Kit (RUO) in NSCLC. METHODS: Study population composed of three patient cohorts with histologically confirmed lung adenocarcinoma (patients with ALK rearrangement, patients with ROS1 rearrangement and patients with wild-type ALK and ROS1)...
September 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28837676/alk-signaling-cascade-confers-multiple-advantages-to-glioblastoma-cells-through-neovascularization-and-cell-proliferation
#19
Risako Chiba, Masashi Akiya, Miki Hashimura, Yasuko Oguri, Madoka Inukai, Atsuko Hara, Makoto Saegusa
Anaplastic lymphoma kinase (ALK), which is a receptor tyrosine kinase, is essentially and transiently expressed in the developing nervous system. Here we examined the functional role of the ALK gene in glioblastomas (GBMs). In clinical samples of GBMs, high ALK expression without gene rearrangements or mutations was frequently observed in perivascular lesions, in contrast to the relatively low expression in the perinecrotic areas, which was positively correlated with N-myc and phosphorylated (p) Stat3 scores and Ki-67 labeling indices...
2017: PloS One
https://www.readbyqxmd.com/read/28834601/cytological-markers-for-predicting-alk-positive-pulmonary-adenocarcinoma
#20
K Miyata, S Morita, H Dejima, N Seki, N Matsutani, M Mieno, F Kondo, Y Soejima, F Tanaka, M Sawabe
BACKGROUND: ALK gene rearrangement is an important class of gene mutations in pulmonary adenocarcinoma. ALK-positive pulmonary adenocarcinoma exhibits characteristic histological features, such as signet ring cell carcinoma (SRCC) and a mucinous cribriform structure. However, when insufficient histological specimens are obtained, ALK-positivity must be predicted based on cytological features. The purpose of this study was to clarify the cytological characteristics of ALK-positive pulmonary adenocarcinoma...
August 23, 2017: Diagnostic Cytopathology
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