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https://www.readbyqxmd.com/read/28811082/correlation-between-molecular-analysis-diagnosis-according-to-the-2015-who-classification-of-unresected-lung-tumours-and-ttf1-expression-in-small-biopsies-and-cytology-specimens-from-344-non-small-cell-lung-carcinoma-patients
#1
Prudence A Russell, Toni-Maree Rogers, Benjamin Solomon, Naveed Alam, Stephen A Barnett, Vivek Rathi, Richard A Williams, Gavin M Wright, Matthew Conron
We investigated correlations between diagnosis according to the 2015 World Health Organization (WHO) classification of unresected lung tumours, molecular analysis and TTF1 expression in small biopsy and cytology specimens from 344 non-small cell lung carcinoma (NSCLC) patients. One case failed testing for EGFR, KRAS and ALK abnormalities and six had insufficient tumour for ALK testing. Overall mutation rate in 343 cases was 48% for the genes tested, with 19% EGFR, 33% KRAS and 4% BRAF mutations, and 5% ALK rearrangements detected...
August 12, 2017: Pathology
https://www.readbyqxmd.com/read/28806935/association-between-charlson-comorbidity-index-score-and-outcome-in-patients-with-stage-iiib-iv-non-small-cell-lung-cancer
#2
Lei Zhao, Lai-Han Leung, Jing Wang, Huihui Li, Juanjuan Che, Lian Liu, Xiaojun Yao, Bangwei Cao
BACKGROUND: This retrospective study investigated the association between the Charlson comorbidity index (CCI) score and the survival of patients with stage IIIB-IV (advanced, non-resectable) non-small cell lung cancer (NSCLC) who also did not have gene mutations in epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK). METHODS: The records of 165 patients (28-80 y, median 61 y) who met the above criteria and were admitted to Beijing Friendship Hospital Capital Medical University from 1 May 2010 to 1 October 2014were reviewed...
August 15, 2017: BMC Pulmonary Medicine
https://www.readbyqxmd.com/read/28806116/systemic-therapy-for-stage-iv-non-small-cell-lung-cancer-american-society-of-clinical-oncology-clinical-practice-guideline-update
#3
Nasser Hanna, David Johnson, Sarah Temin, Sherman Baker, Julie Brahmer, Peter M Ellis, Giuseppe Giaccone, Paul J Hesketh, Ishmael Jaiyesimi, Natasha B Leighl, Gregory J Riely, Joan H Schiller, Bryan J Schneider, Thomas J Smith, Joan Tashbar, William A Biermann, Gregory Masters
Purpose Provide evidence-based recommendations updating the 2015 ASCO guideline on systemic therapy for patients with stage IV non-small-cell lung cancer (NSCLC). Methods The ASCO NSCLC Expert Panel made recommendations based on a systematic review of randomized controlled trials from February 2014 to December 2016 plus the Cancer Care Ontario Program in Evidence-Based Care's update of a previous ASCO search. Results This guideline update reflects changes in evidence since the previous guideline update. Fourteen randomized controlled trials provide the evidence base; earlier phase trials also informed recommendation development...
August 14, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28805673/alk-status-assessment-with-liquid-biopsies-of-lung-cancer-patients
#4
REVIEW
Paul Hofman
Patients with advanced stage non-small cell lung carcinoma (NSCLC) harboring an anaplastic lymphoma kinase ALK gene rearrangement, detected from a tissue sample, can benefit from targeted ALK inhibitor treatment. However, while treatment is initially effective in most cases, relapse or progression occurs due to different resistance mechanisms including mutations in the tyrosine kinase domain of echinoderm microtubule-associated protein-like 4 (EML44)-ALK. The liquid biopsy concept has recently radically changed the clinical care of NSCLC patients, in particular for those harboring an epidermal growth factor receptor (EGFR) gene mutation...
August 12, 2017: Cancers
https://www.readbyqxmd.com/read/28795492/treatment-of-alk-rearranged-non-small-cell-lung-cancer-a-review-of-the-landscape-and-approach-to-emerging-patterns-of-treatment-resistance-in-the-australian-context
#5
M Itchins, P L Chia, S A Hayes, V M Howell, A J Gill, W A Cooper, T John, P Mitchell, M Millward, S J Clarke, B Solomon, N Pavlakis
Since the identification of anaplastic lymphoma kinase (ALK) gene rearrangements in non-small cell lung cancer (NSCLC) in 2005, the treatment of ALK-rearranged NSCLC (ALK+ NSCLC) has evolved at a rapid pace. This molecularly distinct subset of NSCLC has uniquely important biology, clinicopathologic features and mechanisms of drug resistance which impact on the choice of treatment for a patient with this disease. There are multiple ALK tyrosine kinase inhibitors now available in clinical practice with efficacy data continuing to emerge and guide the optimal treatment algorithm...
August 2017: Asia-Pacific Journal of Clinical Oncology
https://www.readbyqxmd.com/read/28794048/hepatitis-c-virus-core-protein-modulates-endoglin-cd105-signaling-pathway-for-liver-pathogenesis
#6
Young-Chan Kwon, Reina Sasaki, Keith Meyer, Ranjit Ray
Endoglin is part of the TGF-β receptor complex and has a crucial role in fibrogenesis and angiogenesis. It is also an important protein for tumor growth, survival, and cancer cell metastasis. In our previous study, we have shown that hepatitis C virus (HCV) infection induces epithelial-mesenchymal transition state (EMT) and cancer stem-like cell (CSC) properties in human hepatocytes. Our array data suggested that endoglin (CD105) mRNA is significantly upregulated in HCV associated CSCs. In this study, we have observed increased endoglin expression on the cell surface of HCV core expressing hepatocellular carcinoma (HepG2) cell line or immortalized human hepatocytes (IHH) and activation of its downstream signaling molecules...
August 9, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28781783/neuroendocrine-carcinoma-of-the-lung-expressing-anaplastic-lymphoma-kinase-on-high-sensitivity-immunohistochemistry-a-case-report
#7
Kotoko Miyoshi, Yasushi Adachi, Hitoshi Nakaji, Akiharu Okamura, Yasuhiro Sakai, Ryuji Hirano, Shinsuke Yahata, Ming Li, Susumu Ikehara
It has been reported that anaplastic lymphoma kinase (ALK) protein is expressed in a proportion of non-small-cell carcinomas (mainly adenocarcinomas). By contrast, high-sensitivity immunohistochemistry (IHC) rarely detects ALK protein expression in neuroendocrine carcinomas (NECs) of the lung, which include small-cell carcinomas and large-cell neuroendocrine carcinomas (LCNECs). We herein present a case of NEC that was identified as ALK-positive via high-sensitivity IHC. A 51-year-old man was diagnosed with small-cell carcinoma in the upper lobe of the right lung...
August 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28781781/responses-to-crizotinib-and-chemotherapy-in-patients-with-lung-adenocarcinoma-harboring-a-concomitant-egfr-mutation-and-alk-gene-rearrangement-a-case-report-and-review-of-the-literature
#8
Yuping Li, Shanshan Su, Guoping Cai, Quan Lin, Ying Zhou, Jinsheng Ouyang, Bicheng Chen, Junru Ye, Xiuling Wu, Chengshui Chen
Previous studies have indicated that, in lung cancers, the gene rearrangement of ALK is mutually exclusive with mutations in the epidermal growth factor receptor (EGFR) gene. However, the coexistence of EML4-ALK fusions and EGFR mutations (double positive) has been occasionally reported, with frequencies ranging from 0-8%. Currently, no consensus standard therapy exists for tumors with double positive mutations. In the present case report, the case is described of a 53-year-old woman with stage IV lung adenocarcinoma, harboring a concomitant EGFR mutation and ALK gene rearrangement, who was refractory to gefitinib administration but demonstrated a good response to crizotinib and pemetrexed chemotherapy...
August 2017: Molecular and Clinical Oncology
https://www.readbyqxmd.com/read/28780976/prospective-clinical-integration-of-an-amplicon-based-next-generation-sequencing-method-to-select-advanced-non-small-cell-lung-cancer-patients-for-genotype-tailored-treatments
#9
Jon Zugazagoitia, Daniel Rueda, Nuria Carrizo, Ana Belen Enguita, David Gómez-Sánchez, Asunción Díaz-Serrano, Elisabeth Jiménez, Antonio Mérida, Rosa Calero, Ricardo Lujan, Eduardo De Miguel, Pablo Gámez, Vicente Díaz-Hellín, Juan Antonio Nuñez, Lara Iglesias, Irene Ferrer, Luis Paz-Ares, Santiago Ponce-Aix
INTRODUCTION: A substantial fraction of non-small-cell lung cancers (NSCLCs) harbor targetable genetic alterations. In this study, we analyzed the feasibility and clinical utility of integrating a next-generation sequencing (NGS) panel into our routine lung cancer molecular subtyping algorithm. PATIENTS AND METHODS: After routine pathologic and molecular subtyping, we implemented an amplicon-based gene panel for DNA analysis covering mutational hot spots in 22 cancer genes in consecutive advanced-stage NSCLCs...
June 23, 2017: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28779874/brief-report-met-exon-14-alterations-and-new-resistance-mutations-to-tyrosine-kinase-inhibitors-risk-of-inadequate-detection-with-current-amplicon-based-ngs-panels
#10
Brigitte Poirot, Ludovic Doucet, Shirine Benhenda, Jérôme Champ, Véronique Meignin, Jacqueline Lehmann-Che
INTRODUCTION: Targeted therapies, as tyrosine kinase inhibitors (TKI), have dramatically improved the treatment of lung adenocarcinoma and detection of activating mutations of genes like EGFR or ALK is now mandatory in clinical setting. However, additional targetable alterations are continuously described and force us to adapt our detection methods. We evaluate here the ability of 8 amplicon-based next generation sequencing (NGS) panels to detect the recently described MET exon 14 alterations or new resistance-mutations to TKI...
August 2, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28776573/pancreatic-intraductal-tubulopapillary-neoplasm-is-genetically-distinct-from-intraductal-papillary-mucinous-neoplasm-and-ductal-adenocarcinoma
#11
Olca Basturk, Michael F Berger, Hiroshi Yamaguchi, Volkan Adsay, Gokce Askan, Umesh K Bhanot, Ahmet Zehir, Fatima Carneiro, Seung-Mo Hong, Giuseppe Zamboni, Esra Dikoglu, Vaidehi Jobanputra, Kazimierz O Wrzeszczynski, Serdar Balci, Peter Allen, Naoki Ikari, Shoko Takeuchi, Hiroyuki Akagawa, Atsushi Kanno, Tooru Shimosegawa, Takanori Morikawa, Fuyuhiko Motoi, Michiaki Unno, Ryota Higuchi, Masakazu Yamamoto, Kyoko Shimizu, Toru Furukawa, David S Klimstra
Intraductal tubulopapillary neoplasm is a relatively recently described member of the pancreatic intraductal neoplasm family. The more common member of this family, intraductal papillary mucinous neoplasm, often carries genetic alterations typical of pancreatic infiltrating ductal adenocarcinoma (KRAS, TP53, and CDKN2A) but additionally has mutations in GNAS and RNF43 genes. However, the genetic characteristics of intraductal tubulopapillary neoplasm have not been well characterized. Twenty-two intraductal tubulopapillary neoplasms were analyzed by either targeted next-generation sequencing, which enabled the identification of sequence mutations, copy number alterations, and selected structural rearrangements involving all targeted (≥300) genes, or whole-exome sequencing...
August 4, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28767387/identification-and-characterization-of-a-novel-scyl3-ntrk1-rearrangement-in-a-colorectal-cancer-patient
#12
Massimo Milione, Elena Ardini, Jason Christiansen, Emanuele Valtorta, Silvio Veronese, Roberta Bosotti, Alessio Pellegrinelli, Adele Testi, Filippo Pietrantonio, Giovanni Fucà, Ge Wei, Danielle Murphy, Salvatore Siena, Antonella Isacchi, Filippo De Braud
In colorectal cancer patients, chromosomal rearrangements involving NTRK1 gene (encoding the TRKA protein) are shown in a small subset of patients and are associated with the constitutive activation of the kinase domain of TRKA. In turn, activated TRKA-fusion proteins are associated with proliferation and survival in colorectal cancer tumors.Here we report the identification and functional characterization of a new SCYL3-NTRK1 fusion gene in a 61-year-old colorectal cancer patient. To our knowledge, this fusion protein has never been previously documented in oncological patients...
July 24, 2017: Oncotarget
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
#13
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
https://www.readbyqxmd.com/read/28758104/liquid-biopsies-in-lung-cancer-time-to-implement-research-technologies-in-routine-care
#14
REVIEW
Linda Köhn, Mikael Johansson, Kjell Grankvist, Jonas Nilsson
Lung cancer is the leading cause of cancer mortality. A substantial progress in the understanding of lung cancer biology has resulted in several promising targeted therapies for advanced disease. Druggable targets today include point mutations such as EGFR, BRAF and re-arrangements in genes such as ALK and ROS1. Liquid biopsies collecting e.g., circulating tumor DNA (ctDNA) reflects overall tumor information and is not biased by analyzing of only a small fraction of the tumor and is always accessible in contrast to the lung cancer tissue...
July 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/28756651/relationship-between-driver-gene-mutations-their-relative-protein-expressions-and-survival-in-non-small-cell-lung-carcinoma-in-macao
#15
Kin Iong Chan, Hong Ting Vong, Lai Fang Sin, Yuk Ching Yip, Xue Yun Zhong, Jian Ming Wen
Objectives We report the status of most common gene mutations in non-small cell lung carcinoma (NSCLC) in Macao, and explore the relationship between each gene mutation and clinicopathologic features and survival. Methods EGFR, KRAS and BRAF mutations were detected by PCR in 122 cases of NSCLC. ALK translocation and MET amplification were detected by fluorescence in situ hybridization (FISH). MET and thyroid transcription factor (TTF-1) were investigated by immunohistochemistry. Clinical data were collected for analyzing their correlation with the gene mutations...
July 29, 2017: Clinical Respiratory Journal
https://www.readbyqxmd.com/read/28756644/the-role-of-anaplastic-lymphoma-kinase-in-pediatric-cancers
#16
REVIEW
Junko Takita
The anaplastic lymphoma kinase (ALK) was initially identified as a fusion partner of the nucleophosmin gene in anaplastic large cell lymphoma (ALCL) with t(2;5)(p23;q35) translocation, and then described with different genetic abnormalities in a number of tumors. Although ALK is known to be involved in the pathogenesis of neuroblastoma through activating mutations or gene amplification, its role in the pathogenesis of other pediatric cancers is still elusive. In addition to neuroblastoma, the high-grade amplification of ALK has been described in a subset of rhabdomyosarcoma cases...
July 30, 2017: Cancer Science
https://www.readbyqxmd.com/read/28753563/pathologic-subtype-defined-prognosis-is-dependent-on-both-tumor-stage-and-status-of-oncogenic-driver-mutations-in-lung-adenocarcinoma
#17
Yu Dong, Ying Li, Bo Jin, Jie Zhang, Jinchen Shao, Hong Peng, Shichun Tu, Baohui Han
Previous studies have shown that the prognosis of lung adenocarcinoma is associated with pathological characterization. In this study, we investigated whether pathology-based prognosis was further influenced by both tumor stage and oncogenic driver mutations. To this end, we recruited a cohort of 465 lung adenocarcinoma patients in China. These patients were classified into 6 pathology-defined subtypes i.e., lepidic-predominant adenocarcinoma (LPA), acinar-predominant adenocarcinoma (APA), papillary-predominant adenocarcinoma (PPA), micropapillary-predominant adenocarcinoma (MPA), solid-predominant adenocarcinoma (SPA), and invasive mucinous adenocarcinoma (IMA)...
July 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28745554/anaplastic-lymphoma-kinase-rearrangements-in-non-small-cell-lung-cancer-novel-applications-in-diagnostics-and-treatment
#18
Rodney E Shackelford, Junaid M Ansari, Eric X Wei, Jonathan S Alexander, James Cotelingam
The ALK gene, first identified as an anaplastic large cell lymphoma driver mutation, is dysregulated in nearly 20 different human malignancies, including 3-7% of non-small-cell lung cancers (NSCLC). In NSCLC, ALK commonly fuses with the EML4, forming a constitutively active tyrosine kinase that drives oncogenic progression. Recently, several ALK-inhibiting drugs have been developed that are more effective than standard chemotherapeutic regimens in treating advanced ALK-positive NSCLC. For this reason, molecular diagnostic testing for dysregulated ALK expression is a necessary part of identifying optimal NSCLC treatment options...
August 2017: Pharmacogenomics
https://www.readbyqxmd.com/read/28744144/alk-and-ros1-concurrent-with-egfr-mutation-in-patients-with-lung-adenocarcinoma
#19
Yanjiao Mao, Shixiu Wu
PURPOSE: The purpose of this study was to explore the frequencies of ALK and ROS1 fusion genes in EGFR-mutant lung adenocarcinoma patients and examine the therapeutic efficacies of EGFR-tyrosine kinase inhibitors (TKIs). MATERIALS AND METHODS: A total of 421 EGFR-mutated patients taking EGFR-TKIs were examined for ALK and ROS1 fusion genes based on reverse transcription-polymerase chain reaction (RT-PCR). Progression-free survival (PFS) and overall survival (OS) were evaluated by the Kaplan-Meier method and compared by the log-rank test...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28743163/alk-and-ros1-testing-on-lung-cancer-cytologic-samples-perspectives
#20
REVIEW
Pasquale Pisapia, Maria D Lozano, Elena Vigliar, Claudio Bellevicine, Francesco Pepe, Umberto Malapelle, Giancarlo Troncone
Cytologic sampling is the mainstay of diagnosing advanced lung cancer. Moreover, to select patients for personalized first-line or second-line treatment, epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) and c-ros oncogene 1 (ROS1) rearrangements are tested on cytologic preparations. Commercially available fluorescence in situ hybridization (FISH) and immunocytochemistry (ICC) assays have primarily been used for the identification of cells harboring ALK or ROS1 gene fusions on histologic rather than cytologic preparations...
July 25, 2017: Cancer
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