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Alk translocation

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https://www.readbyqxmd.com/read/28522751/targeting-fbw7-as-a-strategy-to-overcome-resistance-to-targeted-therapy-in-non-small-cell-lung-cancer
#1
Mingxiang Ye, Yong Zhang, Xinxin Zhang, Jian-Bin Zhang, Pengyu Jing, Liang Cao, Nan Li, Xia Li, Libo Yao, Jian Zhang, Jian Zhang
Inhibition of epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) signaling is highly effective in a subgroup of non-small cell lung cancer (NSCLC) patients with distinct clinicopathological features. However, resistance to EGFR and ALK inhibitors inevitably occurs, and the molecular mechanism underlying resistance is not fully understood. In this study, we report a PI3K/Akt- and MEK/Erk-independent resistance mechanism by which loss of the E3 ubiquitin ligase F-box and WD repeat domain containing 7 (FBW7α) leads to targeted therapy resistance via stabilization of anti-apoptotic protein MCL-1...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28517937/cellular-shuttles-monocytes-macrophages-exhibit-transendothelial-transport-of-nanoparticles-under-physiological-flow
#2
Thomas Moore, Daniel Hauser, Thomas Gruber, Barbara Rothen-Rutishauser, Marco Lattuada, Alke Petri-Fink, Ruth Lyck
A major hurdle in the development of biomedical nanoparticles (NP) is understanding how they interact with complex biological systems and navigate biological barriers to arrive at pathological targets. It is becoming increasingly evident that merely controlling particle physico-chemical properties may not be sufficient to mediate particle biodistribution in dynamic environments. Thus, researchers are increasingly turning towards more complex but likewise more physiological in vitro systems to study particle-cell/particle-system interactions...
May 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28514931/lung-cancer-in-never-smokers-what-are-the-differences
#3
Margarida Dias, Rita Linhas, Sérgio Campainha, Sara Conde, Ana Barroso
INTRODUCTION: Characteristics of never-smokers with lung cancer are still not fully clarified. The aim of this study was to compare never-smokers and ever-smokers with non-small cell lung cancer (NSCLC) regarding patient and tumor characteristics. METHODS: All consecutive newly NSCLC patients with known smoking status diagnosed between 2011 and 2015 were included in this retrospective cohort study. Clinical, histological, and molecular characteristics were compared between ever-smokers and never-smokers...
July 2017: Acta Oncologica
https://www.readbyqxmd.com/read/28507205/a-case-of-metastatic-atypical-neuroendocrine-tumor-with-alk-translocation-and-diffuse-brain-metastases
#4
Victoria E Wang, Lauren Young, Siraj Ali, Vincent A Miller, Anatoly Urisman, John Wolfe, Trever G Bivona, Bertil Damato, Shannon Fogh, Emily K Bergsland
A challenge in precision medicine requires identification of actionable driver mutations. Critical to such effort is the deployment of sensitive and well-validated assays for mutation detection. Although identification of such alterations within the tumor tissue remains the gold standard, many advanced non-small cell lung cancer cases have only limited tissue samples, derived from small biopsies or fine-needle aspirates, available for testing. More recently, noninvasive methods using either circulating tumor cells or tumor DNA (ctDNA) have become an alternative method for identifying molecular biomarkers and screening patients eligible for targeted therapies...
May 15, 2017: Oncologist
https://www.readbyqxmd.com/read/28476735/identification-of-targetable-alk-rearrangements-in-pancreatic-ductal-adenocarcinoma
#5
Aatur D Singhi, Siraj M Ali, Jill Lacy, Andrew Hendifar, Khanh Nguyen, Jamie Koo, Jon H Chung, Joel Greenbowe, Jeffrey S Ross, Marina N Nikiforova, Herbert J Zeh, Inderpal S Sarkaria, Anil Dasyam, Nathan Bahary
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal cancers, with a 5-year survival of 8%. Current therapeutic regimens are largely ineffective and underscore the need for novel treatment strategies. Chromosomal rearrangements involving the anaplastic lymphoma kinase (ALK) gene have been identified in several neoplasms. In addition, ALK protein inhibitors have proven efficacy in patients with ALK-rearranged tumors. However, ALK translocations in PDAC have not been described. Through comprehensive genomic profiling of 3,170 PDACs, we identified 5 cases (0...
May 2017: Journal of the National Comprehensive Cancer Network: JNCCN
https://www.readbyqxmd.com/read/28475519/genomic-assessment-of-blitz-nevi-suggests-classification-as-a-subset-of-blue-nevus-rather-than-spitz-nevus-clinical-histopathologic-and-molecular-analysis-of-18-cases
#6
Maria C Isales, Alexandra M Haugh, Jeffrey Bubley, Anna E Verzì, Bin Zhang, Emily Kudalkar, Christina Y Lee, Pedram Yazdan, Joan Guitart, Pedram Gerami
Blitz nevi/tumors are a distinct subset of melanocytic neoplasia which show mixed morphologic features of Spitz and blue nevus. Genomically, most blue nevi have GNAQ or GNA11 mutations while most Spitzoid neoplasms have either an HRAS mutation or translocations involving MET, ROS, BRAF, ALK1, NTRK1, and RET. The criteria used for the assessment of malignancy in blue and Spitzoid lesions are different, and these lesions have different prognostic markers. In this study, we assess the clinical, morphological, and genomic changes in 18 cases of Blitz nevi/tumors to better characterize this subset of neoplasms and determine their optimal genomic classification...
April 27, 2017: American Journal of Dermatopathology
https://www.readbyqxmd.com/read/28452858/primary-bone-anaplastic-large-cell-lymphoma-masquerading-as-ewing-sarcoma-diagnosis-by-anchored-multiplex-pcr
#7
Susan Swee-Shan Hue, Prasad Iyer, Luke Han Wei Toh, Sudhanshi Jain, Enrica Ee Kar Tan, Kesavan Sittampalam, Derrick Wen Quan Lian, Kenneth Tou En Chang
A 3-year-old boy presented with pathologic fracture of the left proximal femur. Magnetic resonance imaging revealed an aggressive expansile bony mass associated with cortical destruction and surrounding myositis. Computed tomography-guided biopsy revealed a monomorphic small round blue cell tumor by histology. CD99 immunoreactivity and low-level EWSR1 gene translocation by break-apart fluorescent in situ hybridization initially favored a diagnosis of Ewing sarcoma and chemotherapy commenced. Subsequent molecular evaluation by an anchored multiplex polymerase chain reaction-based assay (Archer FusionPlex Sarcoma Panel) revealed a nucleophosmin-anaplastic lymphoma kinase (NPM-ALK) gene fusion...
April 27, 2017: Journal of Pediatric Hematology/oncology
https://www.readbyqxmd.com/read/28451462/pulmonary-adenocarcinoma-with-mucin-production-modulates-phenotype-according-to-common-genetic-traits-a-reappraisal-of-mucinous-adenocarcinoma-and-colloid-adenocarcinoma
#8
Angelica Sonzogni, Fabrizio Bianchi, Alessandra Fabbri, Mara Cossa, Giulio Rossi, Alberto Cavazza, Elena Tamborini, Federica Perrone, Adele Busico, Iolanda Capone, Benedetta Picciani, Barbara Valeri, Ugo Pastorino, Giuseppe Pelosi
Whether invasive mucinous adenocarcinoma (IMA) and colloid adenocarcinoma (ICA) of the lung represent separate tumour entities, or simply lie within a spectrum of phenotypic variability, is worth investigating. Fifteen ICA, 12 IMA, 9 ALK-rearranged adenocarcinomas (ALKA), 8 non-mucinous KRAS-mutated adenocarcinomas (KRASA) and 9 mucinous breast adenocarcinomas (MBA) were assessed by immunohistochemistry for alveolar (TTF1, cytoplasmic MUC1), intestinal (CDX-2, MUC2), gastric (membrane MUC1, MUC6), bronchial (MUC5AC), mesenchymal (vimentin), neuroendocrine (chromogranin A, synaptophysin), sex steroid hormone-related (oestrogen and progesterone receptors), pan-mucinous (HNF4A) and pan-epithelial (keratin 7) lineage biomarkers and by targeted next generation sequencing (TNGS) for 50 recurrently altered cancer genes...
April 2017: Journal of Pathology. Clinical Research
https://www.readbyqxmd.com/read/28409069/efficiency-of-crizotinib-on-an-alk-positive-inflammatory-myofibroblastic-tumor-of-the-central-nervous-system-a-case-report
#9
Anas Chennouf, Elizabeth Arslanian, David Roberge, France Berthelet, Michel Bojanowski, Jean-Paul Bahary, Laura Masucci, Karl Belanger, Marie Florescu, Philip Wong
Inflammatory myofibroblastic tumors (IMT) of the central nervous system (CNS) are rare entities that have a predilection for local recurrences. Approximately half of the inflammatory myofibroblastic tumors contain translocations that result in the over-expression of the anaplastic lymphoma kinase (ALK) gene. We hereby present the case of a patient diagnosed with a left parieto-occipital IMT that recurred after multiple surgeries and radiotherapy. Immuno-histochemical examination of the tumor demonstrated ALK overexpression and the presence of an ALK rearrangement observed in lung cancers...
March 2, 2017: Curēus
https://www.readbyqxmd.com/read/28373005/avelumab-for-patients-with-previously-treated-metastatic-or-recurrent-non-small-cell-lung-cancer-javelin-solid-tumor-dose-expansion-cohort-of-a-multicentre-open-label-phase-1b-trial
#10
James L Gulley, Arun Rajan, David R Spigel, Nicholas Iannotti, Jason Chandler, Deborah J L Wong, Joseph Leach, W Jeff Edenfield, Ding Wang, Hans Juergen Grote, Anja von Heydebreck, Kevin Chin, Jean-Marie Cuillerot, Karen Kelly
BACKGROUND: Avelumab, a human Ig-G1 monoclonal antibody targeting PD-L1 and approved in the USA for the treatment of metastatic Merkel cell carcinoma, has shown antitumour activity and an acceptable safety profile in patients with advanced solid tumours in a dose-escalation phase 1a trial. In this dose-expansion cohort of that trial, we assess avelumab treatment in a cohort of patients with advanced, platinum-treated non-small-cell lung cancer (NSCLC). METHODS: In this dose-expansion cohort of a multicentre, open-label, phase 1 study, patients with progressive or platinum-resistant metastatic or recurrent NSCLC were enrolled at 58 cancer treatment centres and academic hospitals in the USA...
March 31, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28368455/tracking-a-cad-alk-gene-rearrangement-in-urine-and-blood-of-a-colorectal-cancer-patient-treated-with-an-alk-inhibitor
#11
G Siravegna, A Sartore-Bianchi, B Mussolin, A Cassingena, A Amatu, L Novara, M Buscarino, G Corti, G Crisafulli, A Bartolini, F Tosi, M Erlander, F Di Nicolantonio, S Siena, A Bardelli
Background: Monitoring response and resistance to kinase inhibitors is essential to precision cancer medicine, and is usually investigated by molecular profiling of a tissue biopsy obtained at progression. However, tumor heterogeneity and tissue sampling bias limit the effectiveness of this strategy. In addition, tissue biopsies are not always feasible and are associated with risks due to the invasiveness of the procedure. To overcome these limitations, blood-based liquid biopsy analysis has proven effective to non-invasively follow tumor's clonal evolution...
March 24, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28351340/molecular-pathology-of-anaplastic-thyroid-carcinomas-a-retrospective-study-of-144-cases
#12
Benjamin Bonhomme, Yann Godbert, Gaelle Perot, Abir Al Ghuzlan, Stéphane Bardet, Geneviève Belleannée, Lise Crinière, Christine Do Cao, Geneviève Fouilloux, Serge Guyetant, Antony Kelly, Sophie Leboulleux, Camille Buffet, Emmanuelle Leteurtre, Jean-Jacques Michels, Frédérique Tissier, Marie-Elisabeth Toubert, Michel Wassef, Clémence Pinard, Isabelle Hostein, Isabelle Soubeyran
BACKGROUND: Anaplastic thyroid carcinoma (ATC) is a rare tumor, with poorly defined oncogenic molecular mechanisms and limited therapeutic options contributing to its poor prognosis. The aims of this retrospective study were to determine the frequency of anaplastic lymphoma kinase (ALK) translocations and to identify the mutational profile of ATC including TERT promoter mutations. METHODS AND MATERIALS: One hundred and forty-four ATC cases were collected from 10 centers that are a part of the national French network for management of refractory thyroid tumors...
May 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28293986/clear-cell-change-in-thyroid-carcinoma-a-clinicopathologic-and-molecular-study-with-identification-of-variable-genetic-anomalies
#13
Nicole A Cipriani, Shweta Agarwal, Dora Dias-Santagata, William C Faquin, Peter M Sadow
BACKGROUND: Clear-cell carcinoma of the thyroid has been regarded as a variant of follicular (FTC) or papillary (PTC) thyroid carcinoma. Twenty-one primary thyroid carcinomas with clear-cell features, diagnosed in 20 patients (12 female) were identified between 1992 and 2012 (0.5% of in-house thyroid carcinomas). METHODS: Hematoxylin and eosin slides were reviewed. SNaPshot multigene mutational analysis and a translocation panel were successfully performed on 15 of these cases...
April 12, 2017: Thyroid: Official Journal of the American Thyroid Association
https://www.readbyqxmd.com/read/28285687/met-exon-14-skipping-mutation-in-triple-negative-pulmonary-adenocarcinomas-and-pleomorphic-carcinomas-an-analysis-of-intratumoral-met-status-heterogeneity-and-clinicopathological-characteristics
#14
Dohee Kwon, Jaemoon Koh, Sehui Kim, Heounjeong Go, Young A Kim, Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim, Yoon Kyung Jeon, Doo Hyun Chung
OBJECTIVES: MET mutations leading to exon 14 skipping rarely occur in non-small cell lung cancer (NSCLC). Recently, small molecule inhibitors targeting MET mutations showed clinical benefit. However, the clinicopathological characteristics of NSCLC harboring MET mutations, and the correlation among mutations, protein expression, and gene copy number of MET in NSCLC remain unclear. Therefore, we address these issues. MATERIALS AND METHODS: MET exon 14 skipping mutations were evaluated using real-time quantitative reverse-transcription-PCR (qRT-PCR) in 102 triple-negative (i...
April 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28240017/prevalence-of-egfr-and-alk-mutations-in-lung-adenocarcinomas-in-the-levant-area-a-prospective-analysis
#15
Arafat Tfayli, Hind Rafei, Alain Mina, Maya Khalil, Najla Fakhreddin, Rami Mahfouz, Shadi Hamouri, Fadi Farhat, Ziad Salem, Haifa Dbouk, Haider Rabee, Nagi Saghir, Ali Shamseddine, Jawad Makarem, Nizar Bitar, Anas Mougharbil, Hazem Assi, Sally Temraz, Deborah Mukherji, Ismail Matalka, Ghazi Zaatari
Background: A significant percentage of lung adenocarcinomas have a driver mutation. To date, there has been no assessment of the prevalence of such mutations in a Middle Eastern population. The present multicenter prospective study of formalin fixed paraffin embedded (FFPE) tissues from patients diagnosed with lung adenocarcinoma was performed to assess the prevalence of EGFR and ALK mutations in the Levant. Methods: Patients of Middle Eastern origin with lung adenocarcinomas at 10 sites in Lebanon, Jordan and Iraq were prospectively enrolled...
January 1, 2017: Asian Pacific Journal of Cancer Prevention: APJCP
https://www.readbyqxmd.com/read/28237660/pulmonary-adenocarcinoma-with-enteric-differentiation-dissecting-oncogenic-genes-alterations-with-dna-sequencing-and-fish-analysis
#16
Alessia Nottegar, Fabrizio Tabbò, Claudio Luchini, Francesco Guerrera, Marcello Gaudiano, Emilio Bria, Matteo Brunelli, Marco Chilosi, Giorgio Inghirami
BACKGROUND: Pulmonary Adenocarcinoma with Enteric Differentiation (PAED) is a rare subtype of adenocarcinoma of emerging interest, recently introduced in the 2015 WHO classification. However, little is known about major molecular signatures of this class of adenocarcinomas and information about new biomarkers totally lack. METHODS: We examined the NRAS, PIK3CA, EGFR, KRAS and BRAF status through mass spectrometry sequencing and ALK rearrangement by FISH in a series of 8 PAEDs...
February 22, 2017: Experimental and Molecular Pathology
https://www.readbyqxmd.com/read/28188721/pd-l1-over-expression-is-associated-with-a-poor-prognosis-in-asian-non-small-cell-lung-cancer-patients
#17
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
#18
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...
May 15, 2017: Cancer
https://www.readbyqxmd.com/read/28152920/actionable-biomarkers-in-a-non-small-cell-lung-cancer-nsclc-clinical-pathway-cp
#19
(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. This analysis examines the impact of this change...
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
#20
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
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