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Alk translocation

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https://www.readbyqxmd.com/read/28188721/pd-l1-over-expression-is-associated-with-a-poor-prognosis-in-asian-non-small-cell-lung-cancer-patients
#1
Haifeng Xia, Ji Shen, Fang Hu, Shaomu Chen, Haitao Huang, Yaozeng Xu, Haitao Ma
BACKGROUND: The prognostic role of programmed cell death-ligand 1 (PD-L1) in non-small cell lung cancer (NSCLC) remains controversial. This meta-analysis was conducted to clarify the association of PD-L1 with survival in NSCLC patients. METHODS: Relevant studies were collected from PubMed, Embase and Web of Science. Only studies in which PD-L1 expression was detected by immunohistochemical staining in NSCLC patients correlated with patient survival data were included...
February 7, 2017: Clinica Chimica Acta; International Journal of Clinical Chemistry
https://www.readbyqxmd.com/read/28177518/unique-prevalence-of-oncogenic-genetic-alterations-in-young-patients-with-lung-adenocarcinoma
#2
Kosuke Tanaka, Toyoaki Hida, Yuko Oya, Tatsuya Yoshida, Junichi Shimizu, Tetsuya Mizuno, Hiroaki Kuroda, Noriaki Sakakura, Kenichi Yoshimura, Yoshitsugu Horio, Yukinori Sakao, Yasushi Yatabe
BACKGROUND: Lung adenocarcinoma in the young is a rare entity, and the oncogenic genetic alterations (GAs) and clinical characteristics associated with this disease are poorly understood. Conversely, it has been demonstrated that young age at diagnosis defines unique biology in other cancers. For this report, the effects of young age on lung adenocarcinoma are reported. METHODS: The authors retrospectively screened 1746 consecutive patients who were diagnosed with stage I through IV adenocarcinoma between 2009 and 2015 and identified 81 who were aged 40 years or younger at diagnosis...
February 8, 2017: Cancer
https://www.readbyqxmd.com/read/28152920/actionable-biomarkers-in-a-non-small-cell-lung-cancer-nsclc-clinical-pathway-cp
#3
(no author information available yet)
: 155 Background: Oncologists use Via Pathways (VP) to drive standardization to best evidence-based cancer care. VP include guidance for biomarker testing and associated treatments. Practices collaborated to analyze the first line non squamous carcinoma NSCLC VP. An unexpectedly large percentage of treatment decisions captured by oncologists in the VP portal had unknown ALK translocation or EGFR mutation test results. The VP was modified to require input of whether or not the test was ordered...
March 2016: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28112990/alk-gene-alterations-in-cancer-biological-aspects-and-therapeutic-implications
#4
Raffaele Palmirotta, Davide Quaresmini, Domenica Lovero, Franco Silvestris
ALK was first reported in 1994 as a translocation in anaplastic large cell lymphoma and then described with different abnormalities in a number of tumors. Recently, a shortly accumulated biomedical research clarified the numerous biological processes underlying its ability to support cancer development, growth and progression. Advent of precision medicine has finally provided unexpected advances, leading to the development of ALK-targeting inhibitors with superior efficacy as compared with standard chemotherapy regimens, as well as the identification of resistance mechanisms and the creation of 'next-generation' treatments...
February 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28050384/inflammatory-myofibroblastic-tumor-of-the-kidney-a-rare-renal-tumor
#5
Alvin Jose Pothadiyil, Suresh Bhat, Fredrick Paul, Jithesh Mampatta, Mahesh Srinivas
Inflammatory Myofibroblastic Tumour (IMT) or 'pseudotumour' of the kidney is a rare benign tumour of unknown aetiology affecting mostly young adults. A subset of IMT is neoplastic and harbours translocations of activin receptor-like kinase-1 (ALK-1) gene and can recur or rarely metastasize. Presentation varies from an incidentaloma to gross haematuria. Clinical examination and radiological investigations are usually inconclusive. Often, biopsy is inconclusive necessitating a management similar to that of Renal Cell Cancer (RCC)...
November 2016: Journal of Clinical and Diagnostic Research: JCDR
https://www.readbyqxmd.com/read/28039177/differential-protein-stability-and-clinical-responses-of-eml4-alkfusion-variants-to-various-alk-inhibitors-in-advanced-alk-rearranged-non-small-cell-lung-cancer
#6
C G Woo, S Seo, S W Kim, S J Jang, K S Park, J Y Song, B Lee, M W Richards, R Bayliss, D H Lee, J Choi
BACKGROUND: Anaplastic lymphoma kinase (ALK) inhibition using crizotinib has become the standard of care in advanced ALK-rearranged non-small cell lung cancer (NSCLC), but the treatment outcomes and duration of response vary widely. Echinoderm microtubule-associated protein-like 4 (EML4)-ALK is the most common translocation, and the fusion variants show different sensitivity to crizotinib in vitro. However, there are only limited data on the specific EML4-ALK variants and clinical responses of patients to various ALK inhibitors...
December 29, 2016: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28024689/alk-testing-in-non-small-cell-lung-cancer-nsclc-immunohistochemistry-ihc-and-or-fluorescence-in-situ-hybridisation-fish-statement-of-the-germany-society-for-pathology-dgp-and-the-working-group-thoracic-oncology-aio-of-the-german-cancer-society-e-v-stellungnahme
#7
M von Laffert, P Schirmacher, A Warth, W Weichert, R Büttner, R M Huber, J Wolf, F Griesinger, M Dietel, Ch Grohé
The EML4-ALK pathway plays an important role in a significant subset of non-small cell lung cancer patients. Treatment options such as ALK tyrosine kinase inhibitors lead to improved progression free survival and overall survival. These therapeutic options are chosen on the basis of the identification of the underlying genetic signature of the EML-ALK translocation. Efficient and easily accessible testing tools are required to identify eligible patients in a timely fashion. While FISH techniques are commonly used to detect this translocation, the broad implementation of this type of ALK testing into routine diagnostics is not optimal due to technical, structural and financial reasons...
January 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/27988109/receptor-tyrosine-kinases-translocation-partners-in-hematopoietic-disorders
#8
REVIEW
Katelyn N Nelson, Malalage N Peiris, April N Meyer, Asma Siari, Daniel J Donoghue
Receptor tyrosine kinases (RTKs) activate various signaling pathways and regulate cellular proliferation, survival, migration, and angiogenesis. Malignant neoplasms often circumvent or subjugate these pathways by promoting RTK overactivation through mutation or chromosomal translocation. RTK translocations create a fusion protein containing a dimerizing partner fused to an RTK kinase domain, resulting in constitutive kinase domain activation, altered RTK cellular localization, upregulation of downstream signaling, and novel pathway activation...
January 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/27960155/stimulation-of-suicidal-erythrocyte-death-by-ceritinib-treatment-of-human-erythrocytes
#9
Abdulla Al Mamun Bhuyan, Elena Signoretto, Rosi Bissinger, Florian Lang
BACKGROUND/AIMS: The anaplastic lymphoma kinase (ALK) inhibitor ceritinib is utilized for the treatment of ALK positive non-small cell lung carcinoma. Side effects of the drug include decrease of blood hemoglobin concentration. Possible causes of anemia include stimulation of suicidal erythrocyte death or eryptosis, which is characterized by cell shrinkage and cell membrane scrambling with phosphatidylserine translocation to the erythrocyte surface. Signaling of eryptosis includes increase of cytosolic Ca2+ activity ([Ca2+]i), oxidative stress, ceramide, staurosporine sensitive protein kinase C, SB203580 sensitive p38 kinase, D4476 sensitive casein kinase 1, and zVAD sensitive caspases...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27910030/recurrent-cytogenetic-abnormalities-in-non-hodgkin-s-lymphoma-and-chronic-lymphocytic-leukemia
#10
Edmond S K Ma
Characteristic chromosomal translocations are found to be associated with subtypes of B-cell non-Hodgkin lymphoma (NHL), for example t(8;14)(q24;q32) and Burkitt lymphoma, t(14;18)(q32;q21) and follicular lymphoma, and t(11;14)(q13;q32) in mantle cell lymphoma. Only few recurrent cytogenetic aberrations have been identified in the T-cell NHL and the best known is the ALK gene translocation t(2;5)(p23;q35) in anaplastic large cell lymphoma. Since lymph node or other tissue is seldom submitted for conventional cytogenetics study, alternative approaches for translocation detection are polymerase chain reaction (PCR) or fluorescence in situ hybridization (FISH)...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/27879258/nucleophosmin-anaplastic-lymphoma-kinase-npm-alk-the-ultimate-oncogene-and-therapeutic-target
#11
Michael T Werner, Chen Zhao, Qian Zhang, Mariusz A Wasik
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase physiologically expressed by fetal neural cells. However, aberrantly expressed ALK is involved in the pathogenesis of diverse malignancies including distinct types of lymphoma, lung carcinoma, and neuroblastoma. The aberrant ALK expression in non-neural cells results from chromosomal translocations that create novel fusion proteins. These protein hybrids are comprised of the proximal part of a partner gene including its promoter region and the distal part of ALK including coding sequence for the entire kinase domain...
November 22, 2016: Blood
https://www.readbyqxmd.com/read/27877008/detection-of-alk-translocation-in-non-small-cell-lung-carcinoma-nsclc-and-its-clinicopathological-significance-using-the-ventana-immunohistochemical-staining-method-a-single-center-large-scale-investigation-of-1-504-chinese-han-patients
#12
Lin Yang, Yun Ling, Lei Guo, Di Ma, Xuemin Xue, Bingning Wang, Junling Li, Jianming Ying
OBJECTIVE: The novel fully automated immunohistochemistry (IHC) assay-Ventana anaplastic lymphoma kinase (ALK)-D5F3 for screening ALK rearrangements has been approved by China's Food and Drug Administration in 2013, our previous study disclosed a highly specificity and sensitivity nearly 100%, and its efficacy needs to be evaluated in a large cohort of primary lung adenocarcinoma patients, and to compare clinicopathological features with ALK (+) and ALK (-) lung adenocarcinoma. METHODS: A total of 1,504 consecutive surgical lung adenocarcinoma cases of Chinese Han population were collected and re-diagnosed according to the 2011 multidisciplinary classification of lung adenocarcinoma...
October 2016: Chinese Journal of Cancer Research, Chung-kuo Yen Cheng Yen Chiu
https://www.readbyqxmd.com/read/27867615/current-evidence-in-support-of-the-second-generation-anaplastic-lymphoma-kinase-alk-tyrosine-kinase-inhibitor-alectinib-for-the-treatment-of-non-small-cell-lung-cancer-positive-for-alk-translocation
#13
EDITORIAL
https://www.readbyqxmd.com/read/27846861/intraosseous-inflammatory-myofibroblastic-tumor-of-the-mandible-with-a-novel-atic-alk-fusion-mutation-a-case-report
#14
Yoko Tateishi, Koji Okudela, Shigeo Kawai, Takehisa Suzuki, Shigeaki Umeda, Mai Matsumura, Mitomu Kioi, Kenichi Ohashi
BACKGROUND: Inflammatory myofibroblastic tumor (IMT) is a rare low-grade malignant neoplasm with a predilection for children and young adults, and typically arises in the lung, abdominopelvic region, and retroperitoneum. IMTs in the maxillofacial region are extreme rare. Approximately 50% of IMT harbor rearrangements of the anaplastic lymphoma kinase (ALK) gene at 2p23 with various fusion partners. CASE PRESENTATION: We herein report a case of intraosseous IMT of the mandible with a novel ATIC-ALK fusion...
November 15, 2016: Diagnostic Pathology
https://www.readbyqxmd.com/read/27776007/a-comparison-of-morphologic-and-molecular-features-of-braf-alk-and-ntrk1-fusion-spitzoid-neoplasms
#15
Sapna M Amin, Alexandra M Haugh, Christina Y Lee, Bin Zhang, Jeffrey A Bubley, Emily A Merkel, Anna Elisa Verzì, Pedram Gerami
Recent studies have identified translocations involving the kinase domains of ALK, NTRK1, BRAF, RET, and ROS in spitzoid neoplasms. Subsequent studies have also characterized morphologic features corresponding to ALK and NTRK1 translocations. In this study, we sought to further compare morphologic features across a range of 49 genetically defined spitzoid neoplasms with ALK, NTRK1, BRAF, or RET fusions to determine discriminating features. We also compared them with a group of 22 spitzoid neoplasms, which were confirmed to be negative for fusions in ALK, NTRK1, BRAF, and RET...
October 21, 2016: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/27753543/stat3-targeted-treatment-with-silibinin-overcomes-the-acquired-resistance-to-crizotinib-in-alk-rearranged-lung-cancer
#16
Elisabet Cuyàs, Almudena Pérez-Sánchez, Vicente Micol, Javier A Menendez, Joaquim Bosch-Barrera
The signal transducer and activator of transcription 3 (STAT3) has been suggested to play a prominent role in mediating non-small-cell lung cancer (NSCLC) resistance to some tyrosine kinase inhibitor (TKI)-mediated therapies. Using a model of anaplastic lymphoma kinase gene (ALK)-translocated NSCLC with acquired resistance to the ALK TKI crizotinib, but lacking amplifications or mutations in the kinase domain of ALK, we herein present evidence that STAT3 activation is a novel mechanism of crizotinib resistance that involves the upregulation of immune escape and epithelial to mesenchymal transition (EMT) signaling pathways...
December 16, 2016: Cell Cycle
https://www.readbyqxmd.com/read/27747151/a-long-term-survivor-of-non-small-cell-lung-cancer-harboring-concomitant-egfr-mutation-and-alk-translocation
#17
Fumio Imamura, Takako Inoue, Madoka Kimura, Kazumi Nishino, Toru Kumagai
In January 2003, a 55-year old, non-smoking woman visited our hospital to undergo treatment for T4N0M0 pulmonary adenocarcinoma of the left lung. Until death in October 2015, she received over 20 lines of treatment including a second line therapy with gefitinib, which showed long response. In March 2014, she noticed the left axillar lymph node swelling. Aspiration cytology of the lymph node revealed the presence of adenocarcinoma harboring EGFR exon 19 deletion (Ex19del) but not T790M. Concomitant ALK translocation of variant 1 was also detected...
2016: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/27713405/molecular-analysis-of-aggressive-renal-cell-carcinoma-with-unclassified-histology-reveals-distinct-subsets
#18
Ying-Bei Chen, Jianing Xu, Anders Jacobsen Skanderup, Yiyu Dong, A Rose Brannon, Lu Wang, Helen H Won, Patricia I Wang, Gouri J Nanjangud, Achim A Jungbluth, Wei Li, Virginia Ojeda, A Ari Hakimi, Martin H Voss, Nikolaus Schultz, Robert J Motzer, Paul Russo, Emily H Cheng, Filippo G Giancotti, William Lee, Michael F Berger, Satish K Tickoo, Victor E Reuter, James J Hsieh
Renal cell carcinomas with unclassified histology (uRCC) constitute a significant portion of aggressive non-clear cell renal cell carcinomas that have no standard therapy. The oncogenic drivers in these tumours are unknown. Here we perform a molecular analysis of 62 high-grade primary uRCC, incorporating targeted cancer gene sequencing, RNA sequencing, single-nucleotide polymorphism array, fluorescence in situ hybridization, immunohistochemistry and cell-based assays. We identify recurrent somatic mutations in 29 genes, including NF2 (18%), SETD2 (18%), BAP1 (13%), KMT2C (10%) and MTOR (8%)...
October 7, 2016: Nature Communications
https://www.readbyqxmd.com/read/27707887/overcoming-egfr-bypass-signal-induced-acquired-resistance-to-alk-tyrosine-kinase-inhibitors-in-alk-translocated-lung-cancer
#19
Masayoshi Miyawaki, Hiroyuki Yasuda, Tetsuo Tani, Junko Hamamoto, Daisuke Arai, Kota Ishioka, Keiko Ohgino, Shigenari Nukaga, Toshiyuki Hirano, Ichiro Kawada, Katsuhiko Naoki, Yuichiro Hayashi, Tomoko Betsuyaku, Kenzo Soejima
: Activation of the EGFR pathway is one of the mechanisms inducing acquired resistance to anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKI) such as crizotinib and alectinib. Ceritinib is a highly selective ALK inhibitor and shows promising efficacy in non-small cell lung cancers (NSCLC) harboring the ALK gene rearrangement. However, the precise mechanism underlying acquired resistance to ceritinib is not well-defined. This study set out to clarify the mechanism in ALK-translocated lung cancer and to find the preclinical rationale overcoming EGFR pathway-induced acquired resistance to ALK-TKIs...
January 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/27686809/developments-for-personalized-medicine-of-lung-cancer-subtypes-mass-spectrometry-based-clinical-proteogenomic-analysis-of-oncogenic-mutations
#20
Toshihide Nishimura, Haruhiko Nakamura
Molecular therapies targeting lung cancers with mutated epidermal growth factor receptor (EGFR) by EGFR-tyrosin kinase inhibitors (EGFR-TKIs), gefitinib and erlotinib, changed the treatment system of lung cancer. It was revealed that drug efficacy differs by race (e.g., Caucasians vs. Asians) due to oncogenic driver mutations specific to each race, exemplified by gefitinib / erlotinib. The molecular target drugs for lung cancer with anaplastic lymphoma kinase (ALK) gene translocation (the fusion gene, EML4-ALK) was approved, and those targeting lung cancers addicted ROS1, RET, and HER2 have been under development...
2016: Advances in Experimental Medicine and Biology
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