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https://www.readbyqxmd.com/read/27910030/recurrent-cytogenetic-abnormalities-in-non-hodgkin-s-lymphoma-and-chronic-lymphocytic-leukemia
#1
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
#2
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
#3
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
#4
EDITORIAL
https://www.readbyqxmd.com/read/27846861/intraosseous-inflammatory-myofibroblastic-tumor-of-the-mandible-with-a-novel-atic-alk-fusion-mutation-a-case-report
#5
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
#6
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
#7
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...
October 18, 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
#8
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
#9
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
#10
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 epidermal growth factor receptor (EGFR) pathway is one of the mechanisms inducing acquired resistance to anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitors (TKIs) such as crizotinib and alectinib. Ceritinib is a highly selective ALK inhibitor and shows promising efficacy in non-small cell lung cancers (NSCLCs) 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...
October 5, 2016: 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
#11
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
https://www.readbyqxmd.com/read/27614248/combinational-analysis-of-fish-and-immunohistochemistry-reveals-rare-genomic-events%C3%A2-in-alk-fusion-patterns-in-nsclc-that-responds%C3%A2-to-crizotinib-treatment
#12
Wenbin Li, Jing Zhang, Lei Guo, Shannon Chuai, Ling Shan, Jianming Ying
INTRODUCTION: The purpose of this study was to explore the complicated rearrangement mechanisms underlying cases with atypical and negative anaplastic lymphoma receptor tyrosine kinase gene (ALK) fluorescence hybridization (FISH) and positive immunohistochemistry (IHC) results and to stress the importance of combinational assay of these two methods in current pathological diagnosis. METHODS: A total of 3128 NSCLCs were screened for ALK fusions through both FISH analysis and IHC assays with Ventana-D5F3 antibody...
September 8, 2016: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/27597279/erlotinib-has-comparable-clinical-efficacy-to-chemotherapy-in-pretreated-patients-with-advanced-non-small-cell-lung-cancer-nsclc-a-propensity-adjusted-outcomes-research-based-study
#13
P Neumair, L Joos, R Warschkow, A Dutly, S Ess, F Hitz, M Früh, M Brutsche, F Baty, S Krähenbühl, T Cerny, M Joerger
OBJECTIVES: Controversy exists about the integration of erlotinib in patients with EGFR wildtype, advanced NSCLC. MATERIALS AND METHODS: We included patients with advanced NSCLC receiving at least two lines of palliative systemic treatment between January 2005 and December 2014 and not harbouring targetable driver mutations. Primary study endpoint was overall survival (OS), secondary endpoint progression-free survival (PFS). We used Kaplan-Meier statistics, multivariate Cox regression and Propensity score or Inverse Probability Weights (IPW) matching to compare clinical outcome between patients receiving erlotinib in second or further line and those receiving chemotherapy only...
October 2016: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/27592306/nodal-signaling-modulates-the-expression-of-oct-4-via-nuclear-translocation-of-%C3%AE-catenin-in-lung-and-prostate-cancer-cells
#14
Yi-Fei Qi, Long Wu, Zi-Qian Li, Meng-Ling Wu, Hai-Fang Wang, Ka-Ying Chan, Lin-Lin Lu, Shao-Hui Cai, Hong-Sheng Wang, Jun Du
Nodal is a member of transforming growth factor beta (TGF-β) superfamily. Nodal promotes the self-renewal of human cancer stem cells (CSCs) and triggers carcinogenesis of human cancers via an autocrine manner through Smad2/3 pathway. In our study, generation of Nodal-overexpressed cancer cells was constructed, and the effect of Nodal on the stem cell marker Oct-4 was evaluated by overexpression or blocked Nodal/ALKs signaling pathway in non-small cell lung cancer cells A549 and prostate cancer cells PC3. Functionally, Nodal also increased the proliferation via the β-catenin nuclear translocation...
October 15, 2016: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/27587193/-targeted-therapy-and-precision-medicine-more-than-just-words-in-the-treatment-of-lung-cancer
#15
D F Heigener, M Horn, M Reck
Between 10 and 15 % of non-small cell lung cancers (NSCLC) proliferate due to the presence of a so-called driver mutation. This molecular alteration allows the cancer to continue to proliferate and can be deliberately inhibited. In addition to mutations in the epidermal growth factor receptor gene (EGFR) and translocations between the echinoderm microtubule-associated protein-like 4 gene (EML 4) and the anaplastic lymphoma kinase gene (ALK), this applies to ROS1 gene translocations. For the former two alterations, many inhibitors are already available, whereas for ROS1 and other driving mutations the evidence is sparse due to the rare occurrence of these mutations in NSCLC...
December 2016: Der Internist
https://www.readbyqxmd.com/read/27554841/alk-rearrangements-associated-renal-cell-carcinoma-rcc-with-unique-pathological-features-in-an-adult
#16
Marie Jeanneau, Valerie Gregoire, Claude Desplechain, Fabienne Escande, Dan Petre Tica, Sebastien Aubert, Xavier Leroy
We report an exceptional case of renal cell carcinoma (RCC) associated with ALK translocation in an adult. The tumor was located in the left kidney and measured 4cm. The tumor was composed of sheets of large eosinophilic cells with frequently intracytoplasmic vacuoles. The nuclei were large with a nucleolar grade 3. At immunohistochemistry, tumor cells were diffusely positive for PAX8 and vimentin and focally stained with CK7. ALK immunostaining was diffuse and fluorescent in situ hybridization showed a rearrangement of ALK in numerous tumor cells...
November 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/27544536/patients-with-ros1-rearrangement-positive-non-small-cell-lung-cancer-benefit-from-pemetrexed-based-chemotherapy
#17
Zhengbo Song, Haiyan Su, Yiping Zhang
ROS1 gene-rearrangement in non-small-cell lung cancer (NSCLC) patients has recently been identified as a driver gene and benefited from crizotinib treatment. However, no data are available for ROS1-positive NSCLC about chemotherapeutic options and prognostic data. We investigated pemetrexed-based treatment efficacy in ROS1 translocation NSCLC patients and determined the expression of thymidylate synthetase (TS) to provide a rationale for the efficacy results. We determined the ROS1 status of 1750 patients with lung adenocarcinoma...
August 20, 2016: Cancer Medicine
https://www.readbyqxmd.com/read/27535395/resistance-to-therapy
#18
Gabriel Rivera, Heather A Wakelee
Identification of driver mutations in adenocarcinoma of the lung has revolutionized the treatment of this disease. It is now standard of care to look for activating mutations in epidermal growth factor receptor (EGFR), and translocations in anaplastic lymphoma kinase (ALK) or ROS1 in all newly diagnosed adenocarcinoma of the lung, and in many patients with squamous cell carcinoma as well. Recognition of multiple other lung cancer driver mutations has also expanded treatment options. Targeted treatments of these mutations lead to rapid and prolonged responses, but resistance inevitably develops...
2016: Cancer Treatment and Research
https://www.readbyqxmd.com/read/27511159/novel-therapeutic-targets-on-the-horizon-for-lung-cancer
#19
REVIEW
Wan-Ling Tan, Amit Jain, Angela Takano, Evan W Newell, N Gopalakrishna Iyer, Wan-Teck Lim, Eng-Huat Tan, Weiwei Zhai, Axel M Hillmer, Wai-Leong Tam, Daniel S W Tan
Lung cancer is a leading cause of cancer-related mortality worldwide, and is classically divided into two major histological subtypes: non-small-cell lung cancer (NSCLC) and small-cell lung cancer (SCLC). Although NSCLC and SCLC are considered distinct entities with different genomic landscapes, emerging evidence highlights a convergence in therapeutically relevant targets for both histologies. In adenocarcinomas with defined alterations such as EGFR mutations and ALK translocations, targeted therapies are now first-line standard of care...
August 2016: Lancet Oncology
https://www.readbyqxmd.com/read/27509978/clinical-features-of-lung-cancer-in-japanese-patients-aged-under-50
#20
Fumiyasu Igata, Junji Uchino, Masaki Fujita, Akinori Iwasaki, Kentaro Watanabe
The proportion of lung cancer patients under 50 years old is small at approximately 510%, but as with patients older than 50, the number is on the rise. Although lung cancer treatment strategies have undergone extensive transformation in recent years based on the presence or absence of oncogenic driver mutations, there are few reports regarding these mutations in the young or the relationship between clinical setting and prognosis. Therefore, we conducted a study of clinical features in 36 patients under the age of 50 who were diagnosed with primary lung cancer from October 2008 to November 2015...
2016: Asian Pacific Journal of Cancer Prevention: APJCP
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