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Alk translocation

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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
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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...
October 5, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28979145/anaplastic-lymphoma-kinase-inhibition-in-metastatic-non-small-cell-lung-cancer-clinical-impact-of-alectinib
#8
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
#9
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
#10
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
https://www.readbyqxmd.com/read/28931104/-molecular-diagnostics-of-alk-positive-lung-cancer
#11
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/28930717/inhibition-of-erythrocyte-cell-membrane-scrambling-by-asp3026
#12
A Al Mamun Bhuyan, Rosi Bissinger, Hang Cao, Florian Lang
BACKGROUND/AIMS: The anaplastic lymphoma kinase (ALK) inhibitor ASP3026 is in clinical development for the treatment of ALK expressing non-small cell lung carcinoma (NSCLC). ASP3026 is in part effective by inducing apoptosis of tumor cells. Erythrocytes lack mitochondria and nuclei, key organelles in the execution of apoptosis, but are nevertheless able to enter suicidal death or eryptosis, which is characterized by cell membrane scrambling with phosphatidylserine translocation to the cell surface and by cell shrinkage...
2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28895885/anaplastic-lymphoma-kinase-in-cutaneous-malignancies
#13
REVIEW
Severine Cao, Vinod E Nambudiri
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that has been implicated in the pathogenesis of a variety of neoplasms. As suggested by its name, ALK was first described as part of a translocation product in cases of anaplastic large-cell lymphoma, with other genetic and cytogenetic ALK mutations subsequently coming to attention in the development of many other hematologic and solid organ malignancies. ALK has now been shown to play a role in the pathogenesis of several cutaneous malignancies, including secondary cutaneous systemic anaplastic large-cell lymphoma (ALCL) and primary cutaneous ALCL, melanoma, spitzoid tumors, epithelioid fibrous histiocytoma, Merkel cell carcinoma, and basal cell carcinoma...
September 12, 2017: Cancers
https://www.readbyqxmd.com/read/28887531/homogeneity-and-high-concordance-of-alk-translocation-in-primary-lung-adenocarcinoma-and-paired-lymph-node-metastasis
#14
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/28861332/eml4-alk-positive-lung-adenocarcinoma-presenting-an-unusual-metastatic-pattern-in-a-29-year-old-woman-who-is-alive-and-well%C3%A2-in%C3%A2-her-third-year-follow-up-a-case-report
#15
Fatma Tokat, Handan Zeren, Pinar Barut, Sualp Tansan, Umit Ince
Non-small cell lung cancer (NSCLC) is a frequent tumor entity with high mortality. Although several newly discovered chromosomal translocations and mutations opened new horizons for targeted therapy, literature still lacks large series of NSCLC with chromosomal abberations and their correlations with histological and clinical features. We present a case of echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocation positive adenocarcinoma of the lung with an unusual metastatic pattern in a 29-year-old young woman...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28838394/molecular-profiling-in-italian-patients-with-advanced-non-small-cell-lung-cancer-an-observational-prospective-study
#16
Elisa Gobbini, Domenico Galetta, Marcello Tiseo, Paolo Graziano, Antonio Rossi, Emilio Bria, Massimo Di Maio, Giulio Rossi, Vanesa Gregorc, Ferdinando Riccardi, Vieri Scotti, Anna Ceribelli, Lucio Buffoni, Angelo Delmonte, Tindara Franchina, Maria Rita Migliorino, Diego Cortinovis, Salvatore Pisconti, Paola Bordi, Annamaria Catino, Evaristo Maiello, Francesca Arizio, Silvia Novello
OBJECTIVES: Molecular profiling of advanced non-small-cell lung cancer (NSCLC) is recommended according to European and Italian guidelines. However, molecular routine assessment remains still heterogeneous. This observational study aimed to take a picture of the real clinical practice in molecular testing and therapeutic choices in advanced Italian NSCLCs. MATERIALS AND METHODS: This study prospectively enrolled newly diagnosed advanced or recurrent NSCLCs referred to 38 Italian centres, from November 2014 to November 2015...
September 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28802494/toward-a-molecular-genetic-classification-of-spitzoid-neoplasms
#17
REVIEW
Michael T Tetzlaff, Alexandre Reuben, Steven D Billings, Victor G Prieto, Jonathan L Curry
The histopathologic spectrum of Spitzoid neoplasms includes Spitz nevi, atypical Spitz tumors, and Spitzoid melanomas. Advances in molecular genetics have evolved to the point that Spitzoid lesions can now be reasonably classified according to their distinctive molecular-genetic alterations: Spitzoid lesions with (1) 11p amplification and/or HRAS mutations; (2) isolated loss of 6q23 by fluorescence in situ hybridization (FISH); (3) homozygous deletion of 9p21 by FISH; (4) BAP1 loss and BRAFV600 E mutation; (5) translocations involving any of a number of different oncogenic kinase drivers, including ROS1, ALK, NTRK1, NTRK3, MET, BRAF, and RET; and (6) TERT promoter mutations...
September 2017: Clinics in Laboratory Medicine
https://www.readbyqxmd.com/read/28794371/successful-treatment-with-alectinib-for-choroidal-metastasis-in-anaplastic-lymphoma-kinase-rearranged-non-small-cell-lung-cancer
#18
Tomoko Funazo, Kyohei Morita, Naoya Ikegami, Chisato Konishi, Satoshi Nakao, Ryo Ariyasu, Masato Taki, Kazuhiko Nakagawa, Moon Hee Hwang, Chie Yoshimura, Toshiaki Wakayama, Yasuo Nishizaka
Choroidal metastasis is rare in cancer patients and it may cause visual disturbances that reduce their quality of life. In non-small cell lung cancer (NSCLC), targeted therapy against actionable driver mutations has gradually replaced radiotherapy as the treatment of choice for choroidal metastasis. Recently, there have been several case reports of choroidal metastasis in patients with anaplastic lymphoma kinase (ALK)-rearranged NSCLC. We herein report the case of a 40-year-old Japanese woman diagnosed with choroidal metastasis of an ALK-rearranged NSCLC who received alectinib as the first-line chemotherapy...
September 1, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28763691/treatment-of-elderly-patients-or-patients-who-are-performance-status-2-ps2-with-advanced-non-small-cell-lung-cancer-without-epidermal-growth-factor-receptor-egfr-mutations-and-anaplastic-lymphoma-kinase-alk-translocations-still-a-daily-challenge
#19
REVIEW
Chunxia Su, Fei Zhou, Jiqiao Shen, Jing Zhao, Mary O'Brien
Cytotoxic chemotherapy remains the core treatment strategy for patients with advanced non-small cell lung cancer (NSCLC) with tumours that do not have actionable molecular alterations, such as epidermal growth factor receptor (EGFR)-sensitising mutations, anaplastic lymphoma kinase (ALK) translocations or ROS1 translocations. Age and performance status (PS) are two pivotal factors to guide treatment decisions regarding the use of chemotherapy in lung cancer patients. Lung cancer is predominantly a disease of the elderly, with more than two-thirds of patients aged ≥65 years, the current definition of 'elderly'...
September 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28762087/non-small-cell-lung-cancer-nsclc-harboring-alk-translocations-clinical-characteristics-and-management-in-a-real-life-setting-a-french-retrospective-analysis-gfpc-02-14-study
#20
Jean-Bernard Auliac, Isabelle Monnet, Catherine Dubos-Arvis, Anne Marie Chiappa, Nathalie Baize, Suzana Bota, Alain Vergnenegre, Helene Doubre, Chrystele Locher, Acya Bizieux, Gilles Robinet, Christos Chouaid
BACKGROUND: Chromosomal translocations involving the anaplastic lymphoma kinase gene (ALK) are rare oncogenic events found in 3-5% of non-small-cell lung cancers (NSCLC). Limited data have been published on the management of these patients outside clinical trials. OBJECTIVE: To investigate the clinical characteristics and management of patients with NSCLC harboring ALK translocations (ALK+) in a real-life setting in France. METHODS: This multicenter, observational, retrospective study included all NSCLC patients harboring ALK translocations diagnosed in participating centers between January 2012 and December 2014...
July 31, 2017: Targeted Oncology
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