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Alk translocation

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https://www.readbyqxmd.com/read/29343880/novel-application-of-loop-mediated-isothermal-amplification-for-rapid-detection-of-gene-translocation
#1
Ibu Matsuzaki, Hideto Iguchi, Yurina Mikasa, Hiromu Morishita, Katsuya Okuda, Keita Nakaguchi, Yuki Mori, Yoshifumi Iwahashi, Kenji Warigaya, Masakazu Fujimoto, Fumiyoshi Kojima, Shin-Ichi Murata
Identification of fusion genes in cancer is essential for pathological diagnosis and clinical therapy. Although methods for detection of fusion genes, such as fluorescence in situ hybridization (FISH) and real-time polymerase chain reaction (PCR), have been developed in last two decades, these methods are not ideal for detection of these genetic alterations owing to their high cost and time-consuming procedures. In this study, we developed novel application for detection of gene translocations using loop-mediated isothermal amplification (LAMP)...
December 26, 2017: Acta Histochemica et Cytochemica
https://www.readbyqxmd.com/read/29327718/epithelioid-fibrous-histiocytoma-molecular-characterization-of-alk-fusion-partners-in-23-cases
#2
Brendan C Dickson, David Swanson, George S Charames, Christopher Dm Fletcher, Jason L Hornick
Epithelioid fibrous histiocytoma is a rare and distinctive cutaneous neoplasm. Most cases harbor ALK rearrangement and show ALK overexpression, which distinguish this neoplasm from conventional cutaneous fibrous histiocytoma and variants. SQSTM1 and VCL have previously been shown to partner with ALK in one case each of epithelioid fibrous histiocytoma. The purpose of this study was to examine a large cohort of epithelioid fibrous histiocytomas by next-generation sequencing to characterize the nature and prevalence of ALK fusion partners...
January 12, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/29312572/comparison-of-alk-status-between-primary-and-corresponding-lymph-node-metastatic-tumors-in-lung-cancer-patients
#3
Qiqi Gao, Honghai Ma, Bo Wang, Yake Yao, Jianya Zhou, Jianying Zhou
Background: The anaplastic lymphoma kinase (ALK) protein has recently become a promising target in the treatment of non-small cell lung carcinomas(NSCLC) patients with ALK translocation because of the high response rates obtained with an ALK inhibitor. ALK translocations are present in approximately 3-5% of NSCLC patients. According to the literature, little information about the relationship of ALK status between the primary tumor and metastatic sites has been reported. We intended to determine whether the ALK translocations of primary lung cancers are consistent with those in corresponding metastatic lymph node tumors...
December 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29304828/oncogene-addiction-and-radiation-oncology-effect-of-radiotherapy-with-photons-and-carbon-ions-in-alk-eml4-translocated-nsclc
#4
Ying Dai, Quanxiang Wei, Christian Schwager, Janina Hanne, Cheng Zhou, Klaus Herfarth, Stefan Rieken, Kenneth E Lipson, Jürgen Debus, Amir Abdollahi
BACKGROUND: Patients with Echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) positive lung cancer are sensitive to ALK-kinase inhibitors. TAE684 is a potent second generation ALK inhibitor that overcomes Crizotinib resistance. Radiotherapy is an integral therapeutic component of locally advanced lung cancer. Therefore, we sought to investigate the effects of combined radiotherapy and ALK-inhibition via TAE684 in ALK-positive vs. wild type lung cancer cells...
January 5, 2018: Radiation Oncology
https://www.readbyqxmd.com/read/29290199/lung-cancer-with-concomitant-double-gene-mutation
#5
Tao Fan, Xiu-Li Liu, Jun Zhou, Ying-Jie Song, Hong Yang, Ya-Nan Wei
A patient presenting with concomitant epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocation is very rare. We report a non-small cell lung cancer (NSCLC) patient with concomitant EGFR (exon 19-del) mutation and ALK rearrangement. The positron emission tomography-computed tomography (PET-CT) scan revealed a highly metabolic mass lesion in the left lower lobe, measured 5.0 cm in the largest dimension in the S6 segment. Transbronchial lung biopsy (TBLB) showed the pathological diagnosis of invasive adenocarcinoma...
January 2018: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
https://www.readbyqxmd.com/read/29286485/characterization-of-tumor-cells-using-a-medical-wire-for-capturing-circulating-tumor-cells-a-3d-approach-based-on-immunofluorescence-and-dna-fish
#6
Giulia Gallerani, Claudia Cocchi, Martine Bocchini, Filippo Piccinini, Francesco Fabbri
Circulating tumor cells (CTCs) are associated with poor survival in metastatic cancer. Their identification, phenotyping, and genotyping could lead to a better understanding of tumor heterogeneity and thus facilitate the selection of patients for personalized treatment. However, this is hampered because of the rarity of CTCs. We present an innovative approach for sampling a high volume of the patient blood and obtaining information about presence, phenotype, and gene translocation of CTCs. The method combines immunofluorescence staining and DNA fluorescent-in-situ-hybridization (DNA FISH) and is based on a functionalized medical wire...
December 21, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29199679/a-comparative-analysis-of-immunohistochemistry-and-fluorescent-in-situ-hybridization-assay-to-detect-anaplastic-lymphoma-kinase-status-in-lung-adenocarcinoma-cases-a-search-for-a-testing-algorithm
#7
P B Wagle, N A Jambhekar, R Kumar, K Prabhash, C S Pramesh, S B Desai, V Noronha, G Karimundackal, A Shah, A Joshi, S G Laskar, S Jiwnani, T Pai, J P Agarwal
INTRODUCTION: Testing for echinoderm microtubule-associated protein-like 4 (EML4) anaplastic lymphoma kinase (ALK) translocation by fluorescence in situ hybridization (FISH) is well established whereas the Food and Drug Administration (FDA) ALK immunohistochemical (IHC) test is relatively new. AIMS AND OBJECTIVE: The aim of this study is to compare FDA-approved ALK IHC test (D5F3 clone) with the standard ALK FISH test. MATERIALS AND METHODS: A validation and a test arm with 100 and 200 cases of Formalin-Fixed, Paraffin-embedded blocks of lung adenocarcinoma, respectively, comprised the material...
January 2017: Indian Journal of Cancer
https://www.readbyqxmd.com/read/29191776/evaluation-of-ngs-and-rt-pcr-methods-for-alk-rearrangement-in-european-nsclc-patients-results-from-the-etop-lungscape-project
#8
Igor Letovanec, Stephen Finn, Panagiota Zygoura, Paul Smyth, Alex Soltermann, Lukas Bubendorf, Ernst-Jan Speel, Antonio Marchetti, Daisuke Nonaka, Kim Monkhorst, Henrik Hager, Miguel Martorell, Aleksandra Sejda, Richard Cheney, Javier Hernandez-Losa, Eric Verbeken, Walter Weder, Spasenija Savic, Alessia Di Lorito, Atilio Navarro, Enriqueta Felip, Arne Warth, Paul Baas, Peter Meldgaard, Fiona Blackhall, Anne-Marie Dingemans, Hendrik Dienemann, Rafal Dziadziuszko, Johan Vansteenkiste, Cathal O'Brien, Thomas Geiger, Jon Sherlock, Jeoffrey Schageman, Urania Dafni, Roswitha Kammler, Keith Kerr, Erik Thunnissen, Rolf Stahel, Solange Peters
INTRODUCTION: The reported prevalence of ALK rearrangement in NSCLC ranges from 2%-7%. The primary standard diagnostic method is fluorescence in situ hybridization (FISH). Recently, immunohistochemistry (IHC) has also proven to be a reproducible and sensitive technique. Reverse transcriptase-polymerase chain reaction (RT-PCR) has also been advocated and most recently the advent of targeted Next-Generation Sequencing (NGS) for ALK and other fusions has become possible. This study compares ALK evaluation with all 4 techniques in resected NSCLC from the large ETOP Lungscape cohort...
November 27, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/29187209/biodistribution-of-single-and-aggregated-gold-nanoparticles-exposed-to-the-human-lung-epithelial-tissue-barrier-at-the-air-liquid-interface
#9
Estelle Durantie, Dimitri Vanhecke, Laura Rodriguez-Lorenzo, Flavien Delhaes, Sandor Balog, Dedy Septiadi, Joel Bourquin, Alke Petri-Fink, Barbara Rothen-Rutishauser
BACKGROUND: The lung represents the primary entry route for airborne particles into the human body. Most studies addressed possible adverse effects using single (nano)particles, but aerosolic nanoparticles (NPs) tend to aggregate and form structures of several hundreds nm in diameter, changing the physico-chemical properties and interaction with cells. Our aim was to investigate how aggregation might affect the biodistribution; cellular uptake and translocation over time of aerosolized NPs at the air-blood barrier interface using a multicellular lung system...
November 29, 2017: Particle and Fibre Toxicology
https://www.readbyqxmd.com/read/29184678/liquid-biopsy-for-monitoring-anaplastic-lymphoma-kinase-inhibitors-in-non-small-cell-lung-cancer-two-cases-compared
#10
REVIEW
Mariangela Manicone, Maria Chiara Scaini, Maria Grazia Rodriquenz, Antonella Facchinetti, Alfredo Tartarone, Michele Aieta, Rita Zamarchi, Elisabetta Rossi
Three to seven percent of non-small cell lung cancer (NSCLC) patients show anaplastic lymphoma kinase (ALK)-translocation and could be treated with ALK-inhibitors. However, under crizotinib, a first-generation ALK-inhibitor, patients develop drug resistance after a median of 12 months. To overcome crizotinib resistance, several next-generation ALK inhibitors have been developed. In NSCLC, liquid biopsy allowed important improvements in the detection of the epidermal growth factor receptor (EGFR) mutation. The ability of liquid biopsy to detect oncogenic gene/protein fusions is a newly investigated field, and is not routinely applied yet...
October 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/29123416/frequency-and-clinical-relevance-of-egfr-mutations-and-eml4-alk-translocations-in-octogenarians-with-non-small-cell-lung-cancer
#11
Amanda Tufman, Kathrin Kahnert, Thomas Duell, Diego Kauffmann-Guerrero, Katrin Milger, Christian Schneider, Julia Stump, Zulfiya Syunyaeva, Rudolf Maria Huber, Simone Reu
Background: Tyrosine kinase inhibitors (TKIs) have improved response rates in some patients with non-small cell lung cancer (NSCLC), and testing for EGFR mutation and ALK translocation is recommended for all patients with advanced lung adenocarcinoma. The frequency of driver mutations in elderly and very elderly patients has not been described. Patients and methods: We reviewed EGFR and ALK in patients over the age of 70 years diagnosed and treated at our center in 2015 (subgroups: 70-74, 75-79 and >80 years)...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29119148/brigatinib-for-the-treatment-of-alk-positive-advanced-non-small-cell-lung-cancer-patients
#12
A Passaro, A Prelaj, A Pochesci, G Spitaleri, G Rossi, E Del Signore, C Catania, F de Marinis
Brigatinib (AP-26113, Alunbrig) is a second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) that is highly active in non-small cell lung cancer (NSCLC) harboring ALK translocation. Brigatinib was found to be very active against different ALK resistance mutations that mediate acquired resistance biology processes, particularly G1269A ALK C1156Y, I1171S/T, V1180L and others. Different clinical trials evaluated the activity of brigatinib in crizotinib-resistant patients, confirming high activity with durable response not only in parenchymal disease, but also in intracranial disease...
August 2017: Drugs of Today
https://www.readbyqxmd.com/read/29110845/an-international-epidemiological-analysis-of-young-patients-with-non-small-cell-lung-cancer-adujov-clicap
#13
Luis Corrales-Rodríguez, Oscar Arrieta, Luis Mas, Renata Báez-Saldaña, Omar Castillo-Fernández, Normand Blais, Claudio Martín, Melissa Juárez, Priyanka Khanna, Allan Ramos-Esquivel, Ludwing Bacon, Leonardo Rojas, Beatriz Wills, George Oblitas, María Angelina Pérez, Mauricio Cuello, Andrés Felipe Cardona
BACKGROUND: A proportion of patients with NSCLC is diagnosed at 40 years or younger. These patients tend to be never-smokers, usually present with stage IV adenocarcinoma, and have somatic genomic alterations. Few studies have documented and analyzed epidemiological characteristics of this population. MATERIALS AND METHODS: We performed an international epidemiological analysis of 389 young patients with NSCLC. Data was collected from centers participating in the Latin American Consortium for Lung Cancer Research (AduJov-CLICaP)...
November 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29100434/oncogenic-driver-mutations-treatment-and-egfr-tki-resistance-in-a-caucasian-population-with-non-small-cell-lung-cancer-survival-in-clinical-practice
#14
Martin Faehling, Birgit Schwenk, Sebastian Kramberg, Robert Eckert, Anna-Lena Volckmar, Albrecht Stenzinger, Jörn Sträter
Introduction: Oncogenic driver mutations activating EGFR, ALK, or BRAF in NSCLC predict sensitivity to specific tyrosine-kinase inhibitors (TKIs). We provide data on prevalence, treatment and survival of driver-mutation positive NSCLC in a predominantly Caucasian population in routine clinical practice. Patients and Methods: NSCLC patients diagnosed from 2006-2015 with an EGFR-test result were included (n=265). Testing for EGFR, ALK, or BRAF was performed if specific TKI therapy was considered...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29081033/the-presence-of-alk-alterations-and-clinical-relevance-of-crizotinib-treatment-in-pediatric-solid-tumors
#15
Luca Felkai, Rita Bánusz, Ilona Kovalszky, Zoltán Sápi, Miklós Garami, Gergő Papp, Katalin Karászi, Edit Varga, Monika Csóka
Soft tissue sarcomas (STS) and neuroblastomas (NBL), are childhood malignancies still associated with poor prognoses despite the overall improvement in childhood tumor survival of the past decades. Anaplastic lymphoma kinase (ALK) inhibition is promising new strategy to improve the outcome of these pediatric tumors. Eighteen histologic samples of pediatric STS and 19 NBL patients were analyzed for ALK abnormalities using fluorescent in situ hybridization (FISH) with break-apart probes and immunohistochemistry (IHC)...
October 28, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/29066915/molecular-alterations-and-clinical-prognostic-factors-for-cholangiocarcinoma-in-thai-population
#16
N Trachu, E Sirachainan, N Larbcharoensub, W Rattanadech, S Detarkom, N Monnamo, K Kamprerasart, D MunTham, C Sukasem, T Reungwetwattana
This study explores genomic alterations in cholangiocarcinoma (CCC) tissues in Thai patients. We identified and reviewed the records of patients who had been diagnosed with CCC and for whom sufficient tumor samples for DNA and RNA extraction were available in our database. The specimens were explored for EGFR, KRAS, BRAF, and PIK3CA mutations and ROS1 translocation in 81 samples. Immunohistochemistry staining for HER2, ALK, and Ki-67 expression was tested in 74 samples. Prevalence of EGFR, KRAS, and PIK3CA mutations in this study was 21%, 12%, and 16%, respectively...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28987389/environmental-tobacco-smoke-exposure-and-egfr-and-alk-alterations-in-never-smokers-lung-cancer-results-from-the-lcrins-study
#17
MULTICENTER STUDY
María Torres-Durán, Alberto Ruano-Ravina, Karl T Kelsey, Isaura Parente-Lamelas, Virginia Leiro-Fernández, Ihab Abdulkader, Mariano Provencio, José Abal-Arca, Olalla Castro-Añón, Carmen Montero-Martínez, Iria Vidal-García, Margarita Amenedo, Antonio Golpe-Gómez, Cristina Martínez, Rosirys Guzmán-Taveras, María José Mejuto-Martí, Alberto Fernández-Villar, Juan Miguel Barros-Dios
Environmental tobacco smoke (ETS) exposure is a main risk factor of lung cancer in never smokers. Epidermal Growth Factor Receptor (EGFR) mutations and ALK translocations are more frequent in never smokers' lung cancer than in ever-smokers. We performed a multicenter case-control study to assess if ETS exposure is associated with the presence of EGFR mutations and its types and if ALK translocations were related with ETS exposure. All patients were never smokers and had confirmed lung cancer diagnosis. ETS exposure during childhood showed a negative association on the probability of EGRF mutation though not significant...
December 28, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28979145/anaplastic-lymphoma-kinase-inhibition-in-metastatic-non-small-cell-lung-cancer-clinical-impact-of-alectinib
#18
REVIEW
Ittai B Muller, Adrianus J de Langen, Elisa Giovannetti, Godefridus J Peters
A subset of non-small cell lung cancer (NSCLC) tumors (5%) harbors an anaplastic lymphoma kinase (ALK) translocation that drives tumorigenesis. The clinically approved first-line treatment crizotinib specifically inhibits ALK and improves progression-free survival (PFS) in treated and untreated patients by 4 months compared to standard chemotherapy. While some patients relapse after crizotinib treatment due to resistance mutations in ALK, second-generation ALK inhibitors effectively induce tumor response and prolong PFS...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28955002/the-case-of-double-primary-lung-adenocarcinomas-with-an-egfr-mutation-and-alk-translocation-successfully-treated-with-alectinib-at-the-post-surgical-recurrence
#19
Yoshio Tsunezuka, Nobuyoshi Tanaka, Hideki Fujimori, Yuki Togashi, Satoko Baba, Kengo Takeuchi, Kazuyoshi Katayanagi, Hiroshi Kurumaya, Hironori Kitade, Shinji Atagi, Seiji Yano
A 36-year-old male was found two nodules in the right lower lobe of the lung. After the surgical resection, both lesions were diagnosed as invasive adenocarcinomas. One lesion was primarily lepidic growth component with EGFR-L858R mutation, and the other was micropapillary component with ALK translocation accompanying mediastinal lymphnode metastases. While he experienced disease recurrence, the disease was controlled by an ALK inhibitor, given based on the findings of surgical specimens. This is the first case who had two simultaneous lung cancers with EGFR mutation and ALK translocation in each respective lesion, and was successfully treated with ALK inhibitor at the post-surgical recurrence...
2017: Journal of Medical Investigation: JMI
https://www.readbyqxmd.com/read/28943409/interleukin-1-%C3%AE-induced-smad2-3-linker-modifications-are-tak1-dependent-and-delay-tgf%C3%AE-signaling-in-primary-human-mesenchymal-stem-cells
#20
Guus G van den Akker, Henk M van Beuningen, Elly L Vitters, Marije I Koenders, Fons A van de Loo, Peter L van Lent, Esmeralda N Blaney Davidson, Peter M van der Kraan
BACKGROUND: Chondrogenic differentiation of mesenchymal stem cells (MSC) requires transforming growth factor beta (TGFβ) signaling. TGFβ binds to the type I receptor activin-like kinase (ALK)5 and results in C-terminal SMAD2/3 phosphorylation (pSMAD2/3C). In turn pSMAD2/3C translocates to the nucleus and regulates target gene expression. Inflammatory mediators are known to exert an inhibitory effect on MSC differentiation. In this study we investigated the effect of interleukin 1 β (IL1β) on SMAD2/3 signaling dynamics and post-translational modifications...
December 2017: Cellular Signalling
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