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https://www.readbyqxmd.com/read/28546520/-omic-approach-in-non-smoker-female-with-lung-squamous-cell-carcinoma-pinpoints-to-germline-susceptibility-and-personalized-medicine
#1
Margherita Baldassarri, Chiara Fallerini, Francesco Cetta, Marco Ghisalberti, Cristiana Bellan, Simone Furini, Ottavia Spiga, Sergio Crispino, Giuseppe Gotti, Francesca Ariani, Piero Paladini, Alessandra Renieri, Elisa Frullanti
Purpose: Lung cancer is strongly associated to tobacco smoking. However, global statistics estimate that in females the proportion of lung cancer cases that is unrelated to tobacco smoking reaches fifty percent, making questionable the etiology of the disease. Materials and Methods: A never-smoker female with primary EGFR/KRAS/ALK-negative squamous cell carcinoma of the lung and their normal sibs were subjected to a novel integrative "omic" approach using a pedigree-based model for discovering genetic factors leading to cancer in the absence of well-known environmental trigger...
May 26, 2017: Cancer Research and Treatment: Official Journal of Korean Cancer Association
https://www.readbyqxmd.com/read/28544061/survival-difference-according-to-mutation-status-in-a-prospective-cohort-study-of-australian-patients-with-metastatic-non-small-cell-lung-carcinoma-nsclc
#2
Lavinia Tan, Marliese Alexander, Ann Officer, Michael MacManus, Linda Mileshkin, Ross Jennens, Dishan Herath, Richard de Boer, Stephen B Fox, David Ball, Benjamin Solomon
BACKGROUND AND OBJECTIVE: Non-small cell lung cancer (NSCLC) is a heterogeneous disease comprising not only different histologic subtypes but also different molecular subtypes. Our objective is to describe the frequency of oncogenic drivers in patients with metastatic NSCLC, the proportion of patients tested and survival difference according to mutation status in a single-institution study. METHODS: Metastatic NSCLC patients enrolled onto a prospective Thoracic Malignancies Cohort (TMC) Study between July 2012 and August 2016 were selected...
May 24, 2017: Internal Medicine Journal
https://www.readbyqxmd.com/read/28539465/utility-of-genomic-assessment-of-blood-derived-circulating-tumor-dna-ctdna-in-patients-with-advanced-lung-adenocarcinoma
#3
Maria Schwaederle, Sandip P Patel, Hatim Husain, Megumi Ikeda, Richard Lanman, Kimberly C Banks, AmirAli Talasaz, Lyudmila Bazhenova, Razelle Kurzrock
<p>Genomic alterations in blood-derived circulating tumor DNA (ctDNA) from patients with non-small cell lung adenocarcinoma (NSCLC) were ascertained and correlated with clinical characteristics and therapeutic outcomes.</p> <br /><br />Experimental Design: Comprehensive plasma ctDNA testing was performed in 88 consecutive patients; 34 also had tissue next generation sequencing; 29, other forms of genotyping; and 25 (28.4%) had no tissue molecular tests because of inadequate tissue or biopsy contraindications...
May 24, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28535796/identification-of-eml4-alk-as-an-alternative-fusion-gene-in-epithelioid-inflammatory-myofibroblastic-sarcoma
#4
Quan Jiang, Han-Xing Tong, Ying-Yong Hou, Yong Zhang, Jing-Lei Li, Yu-Hong Zhou, Jing Xu, Jiong-Yuan Wang, Wei-Qi Lu
BACKGROUND: Known as solid tumors of intermediate malignant potential, most inflammatory myofibroblastic tumors (IMTs) are treatable as long as the tumor is en-bloc resected. However, in some cases, the tumors have recurred and grown rapidly after successful surgery. Some of these tumors were classified as an epithelioid inflammatory myofibroblastic sarcoma (EIMS). Most previously reported EIMSs have been caused by RANBP2-ALK fusion gene. We herein report an EIMS case caused by an EML4-ALK fusion gene...
May 23, 2017: Orphanet Journal of Rare Diseases
https://www.readbyqxmd.com/read/28534101/evaluation-of-alk-gene-rearrangement-in-central-nervous-system-metastases-of-non-small-cell-lung-cancer-using-two-step-rt-pcr-technique
#5
M Nicoś, P Krawczyk, K Wojas-Krawczyk, A Bożyk, B Jarosz, M Sawicki, T Trojanowski, J Milanowski
PURPOSE: RT-PCR technique has showed a promising value as pre-screening method for detection of mRNA containing abnormal ALK sequences, but its sensitivity and specificity is still discussable. Previously, we determined the incidence of ALK rearrangement in CNS metastases of NSCLC using IHC and FISH methods. MATERIALS: We evaluated ALK gene rearrangement using two-step RT-PCR method with EML4-ALK Fusion Gene Detection Kit (Entrogen, USA). The studied group included 145 patients (45 females, 100 males) with CNS metastases of NSCLC and was heterogeneous in terms of histology and smoking status...
May 22, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28521447/ct-guided-aspiration-lung-biopsy-for-egfr-and-alk-gene-mutation-analysis-of-lung-cancer
#6
Weisheng Lian, Yong Ouyang
The present study investigated the rates of detection and the positive rates of computed tomography (CT)-guided aspiration of lung biopsy for epidermal growth factor receptor (EGFR) gene and anaplastic lymphoma kinase (ALK) gene, and analyzed the relationship between gene mutation and clinical characteristics to improve the rate of related factors of gene detection. The clinical data and CT-guided aspiration biopsy specimen of 250 patients with lung cancer. Data showed that the rate of EGFR gene mutation was 41...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521285/arid1b-alterations-identify-aggressive-tumors-in-neuroblastoma
#7
Soo Hyun Lee, Jung-Sun Kim, Siyuan Zheng, Jason T Huse, Joon Seol Bae, Ji Won Lee, Keon Hee Yoo, Hong Hoe Koo, Sungkyu Kyung, Woong-Yang Park, Ki Woong Sung
Targeted panel sequencing was performed to determine molecular targets and biomarkers in 72 children with neuroblastoma. Frequent genetic alterations were detected in ALK (16.7%), BRCA1 (13.9%), ATM (12.5%), and PTCH1 (11.1%) in an 83-gene panel. Molecular targets for targeted therapy were identified in 16 of 72 patients (22.2%). Two-thirds of ALK mutations were known to increase sensitivity to ALK inhibitors. Sequence alterations in ARID1B were identified in 5 of 72 patients (6.9%). Four of five ARID1B alterations were detected in tumors of high-risk patients...
April 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28516197/optimized-immunohistochemistry-using-the-d5f3-antibody-provides-a-reliable-test-for-identification-of-alk-positive-lung-adenocarcinomas
#8
Gian Luca Rampioni Vinciguerra, Stefania Scarpino, Benedetto Pini, Claudia Cippitelli, Flavio Fochetti, Luigi Ruco
We used optimized immunohistochemistry (IHC) with the D5F3 antibody for detection of tumours in a prospective study of 307 pulmonary adenocarcinomas. Cases positive by IHC (1+, 2+, 3+) were further investigated by fluorescent in situ hybridization (FISH). Of 307 cases, 22 (7.2%) were moderately intensely positive (2+/3+); 18 of these (82%) were also positive by FISH. Of the four IHC-positive/FISH-negative cases, one was unsuitable for FISH and three had abnormalities of the ALK gene. All cases with weak reactivity with D5F3 (1+) were FISH-negative...
May 17, 2017: Virchows Archiv: An International Journal of Pathology
https://www.readbyqxmd.com/read/28514730/circulating-micrornas-as-novel-biomarkers-of-alk-positive-nonsmall-cell-lung-cancer-and-predictors-of-response-to-crizotinib-therapy
#9
Liang-Liang Li, Li-Li Qu, Han-Jiang Fu, Xiao-Fei Zheng, Chuan-Hao Tang, Xiao-Yan Li, Jian Chen, Wei-Xia Wang, Shao-Xing Yang, Lin Wang, Guan-Hua Zhao, Pan-Pan Lv, Min Zhang, Yang-Yang Lei, Hai-Feng Qin, Hong Wang, Hong-Jun Gao, Xiao-Qing Liu
Circulating microRNAs are potential diagnostic and predictive biomarkers, but have not been investigated for patients with anaplastic lymphoma kinase (ALK)-positive lung cancer. In this exploratory study, we sought to identify potential plasma biomarkers for ALK-positive non-small cell lung cancer (NSCLC). A microRNA microarray was used to select ALK-related microRNAs in ALK-positive NSCLC (n = 3), ALK-negative NSCLC (n = 3), and healthy subjects (n = 3). Plasma levels of 21 microRNAs were differentially expressed for ALK-positive and ALK-negative NSCLC, including 14 down-regulated and 7 up-regulated microRNAs...
April 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28513466/non-small-cell-lung-cancer-mutations-targeted-and-combination-therapy
#10
Justyna Kutkowska, Irena Porębska, Andrzej Rapak
Year after year, a growing number of cases of non-small cell lung cancer (NSCLC), mostly caused by smoking, have been noted. Most patients die because of the late detection of cancer and tumor resistance to treatment with cytostatics. Treatment of patients with advanced NSCLC is impeded by the low sensitivity of the tumor to cytostatic agents and the co-existence of many diseases, which substrate is, like lung cancer, cigarette smoking. Along with the development of molecular biology, targeted therapy has started to be used, affecting specific signaling pathways involved in the processes of oncogenesis...
May 17, 2017: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/28512256/concomitant-eml4-alk-rearrangement-and-egfr-mutation-in-non-small-cell-lung-cancer-patients-a-literature-review-of-100-cases
#11
REVIEW
Giuseppe Lo Russo, Martina Imbimbo, Giulia Corrao, Claudia Proto, Diego Signorelli, Milena Vitali, Monica Ganzinelli, Laura Botta, Nicoletta Zilembo, Filippo de Braud, Marina Chiara Garassino
The discovery of EGFR mutations and EML4-ALK gene rearrangements has radically changed the therapeutic scenario for patients with advanced non-small cell lung cancer. ALK and EGFR tyrosine-kinase inhibitors showed better activity and efficacy than standard chemotherapy in the first and second line treatment settings, leading to a clear advantage in overall survival of advanced non small cell lung cancer patients harboring these genetic alterations.Historically the coexistence of EGFR mutations and EML4-ALK rearrangements in the same tumor has been described as virtually impossible...
April 26, 2017: Oncotarget
https://www.readbyqxmd.com/read/28512244/engineering-and-functional-characterization-of-fusion-genes-identifies-novel-oncogenic-drivers-of-cancer
#12
Hengyu Lu, Nicole Villafane, Turgut Dogruluk, Caitlin L Grzeskowiak, Kathleen Kong, Yiu Huen Tsang, Oksana Zagorodna, Angeliki Pantazi, Lixing Yang, Nicholas J Neill, Young Won Kim, Chad J Creighton, Roel G Verhaak, Gordon B Mills, Peter Park, Raju S Kucherlapati, Kenneth L Scott
Oncogenic gene fusions drive many human cancers, but tools to more quickly unravel their functional contributions are needed. Here we describe methodology permitting fusion gene construction for functional evaluation. Using this strategy, we engineered the known fusion oncogenes, BCR-ABL1, EML4-ALK, and ETV6-NTRK3, as well as 20 previously uncharacterized fusion genes identified in TCGA datasets. In addition to confirming oncogenic activity of the known fusion oncogenes engineered by our construction strategy, we validated five novel fusion genes involving MET, NTRK2, and BRAF kinases that exhibited potent transforming activity and conferred sensitivity to FDA-approved kinase inhibitors...
May 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28507793/composite-biomarkers-defined-by-multiparametric-immunofluorescence-analysis-identify-alk-positive-adenocarcinoma-as-a-potential-target-for-immunotherapy
#13
Hélène Roussel, Eléonore De Guillebon, Lucie Biard, Marion Mandavit, Laure Gibault, Elisabeth Fabre, Martine Antoine, Paul Hofman, Michèle Beau-Faller, Hélène Blons, Claire Danel, Françoise Le Pimpec Barthes, Alain Gey, Clémence Granier, Marie Wislez, Pierre Laurent-Puig, Stéphane Oudard, Patrick Bruneval, Cécile Badoual, Jacques Cadranel, Eric Tartour
Anaplastic lymphoma kinase (ALK) inhibitors have been successfully developed for non-small cell lung carcinoma (NSCLC) displaying chromosomal rearrangements of the ALK gene, but unfortunately resistance invariably occurs. Blockade of the PD-1-PD-L1/2 inhibitory pathway constitutes a breakthrough for the treatment of NSCLC. Some predictive biomarkers of clinical response to this therapy are starting to emerge, such as PD-L1 expression by tumor/stromal cells and infiltration by CD8(+) T cells expressing PD-1...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28490045/uterine-inflammatory-myofibroblastic-tumors-frequently-harbor-alk-fusions-with-igfbp5-and-thbs1
#14
Josh D Haimes, Colin J R Stewart, Brian A Kudlow, Brady P Culver, Bo Meng, Eleanor Koay, Ann Whitehouse, Nichola Cope, Jen-Chieh Lee, Tony Ng, W Glenn McCluggage, Cheng-Han Lee
Inflammatory myofibroblastic tumor (IMT) can occur in a number of anatomic sites, including the uterus. Like its soft tissue counterpart, uterine IMT frequently expresses ALK and harbors ALK genetic rearrangements. The aim of this study is to fully characterize the genetic fusions that occur in uterine IMT. We studied 11 uterine IMTs with typical histology and 8 uterine myxoid smooth muscle tumors (5 leiomyomas, 1 smooth muscle tumor of uncertain malignant potential, and 2 leiomyosarcomas) in which the differential of IMT was considered, using a RNA-sequencing-based fusion assay to detect genetic fusions involving ALK, ROS1, RET, NTRK1/3, and other genes...
June 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28489587/ngs-based-identification-of-mutational-hotspots-for-targeted-therapy-in-anaplastic-thyroid-carcinoma
#15
Vera Tiedje, Saskia Ting, Thomas Herold, Sarah Synoracki, Soeren Latteyer, Lars C Moeller, Denise Zwanziger, Martin Stuschke, Dagmar Fuehrer, Kurt Werner Schmid
CONTEXT: Anaplastic thyroid carcinoma (ATC) represents one of the most aggressive carcinomas with no consistent survival benefit when treated with conventional radiochemotherapy. Approaches targeting "oncogene addiction" of ATC are increasingly explored and first promising results have been reported in single case studies. OBJECTIVE: To determine the prevalence of mutations in known thyroid oncogenes and signalling pathways amendable to targeted therapy in a large cohort of ATC...
April 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28477056/discovery-of-potent-alk-inhibitors-using-pharmacophore-informatics-strategy
#16
Nivya James, K Ramanathan
Anaplastic lymphoma kinase is a tyrosine kinase receptor protein belonging to insulin receptor superfamily. Gene fusions in anaplastic lymphoma kinase are associated with non-small cell lung cancer development. Hence, they are of immense importance in targeted therapies. Thus, for the treatment of non-small cell lung cancer, effective anaplastic lymphoma kinase inhibitors are of great significance. Therefore, our objective is to find hit compounds that could have better inhibitory activity than the existing anaplastic lymphoma kinase inhibitors...
May 6, 2017: Cell Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28476735/identification-of-targetable-alk-rearrangements-in-pancreatic-ductal-adenocarcinoma
#17
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/28475456/brigatinib-in-patients-with-crizotinib-refractory-anaplastic-lymphoma-kinase-positive-non-small-cell-lung-cancer-a-randomized-multicenter-phase-ii-trial
#18
Dong-Wan Kim, Marcello Tiseo, Myung-Ju Ahn, Karen L Reckamp, Karin Holmskov Hansen, Sang-We Kim, Rudolf M Huber, Howard L West, Harry J M Groen, Maximilian J Hochmair, Natasha B Leighl, Scott N Gettinger, Corey J Langer, Luis G Paz-Ares Rodríguez, Egbert F Smit, Edward S Kim, William Reichmann, Frank G Haluska, David Kerstein, D Ross Camidge
Purpose Most crizotinib-treated patients with anaplastic lymphoma kinase gene ( ALK)-rearranged non-small-cell lung cancer (ALK-positive NSCLC) eventually experience disease progression. We evaluated two regimens of brigatinib, an investigational next-generation ALK inhibitor, in crizotinib-refractory ALK-positive NSCLC. Patients and Methods Patients were stratified by brain metastases and best response to crizotinib. They were randomly assigned (1:1) to oral brigatinib 90 mg once daily (arm A) or 180 mg once daily with a 7-day lead-in at 90 mg (180 mg once daily [with lead-in]; arm B)...
May 5, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28472177/ubiquitin-carboxyl-terminal-esterase-l1-uchl1-is-associated-with-stem-like-cancer-cell-functions-in-pediatric-high-grade-glioma
#19
Patricia C Sanchez-Diaz, Judy C Chang, Emily S Moses, Tu Dao, Yidong Chen, Jaclyn Y Hung
Pediatric high-grade gliomas represent 8-12% of all primary tumors of the nervous system in children. Five-year survival for these pediatric aggressive tumors is poor (15-35%) indicating the need to develop better treatments for pediatric high-grade gliomas. In this work we used SF188 and SJ-GBM2 cell lines to study the function of the ubiquitin carboxyl-terminal esterase L1 (UCHL1), a deubiquitinase de-regulated in several cancers, in pediatric high-grade gliomas. UCHL1 depletion in SF188 and SJ-GBM2 glioma cells was associated with decreased cell proliferation and invasion, along with a reduced ability to grow in soft agar and to form spheres (i...
2017: PloS One
https://www.readbyqxmd.com/read/28471124/multiplex-genomic-test-of-mutation-and-fusion-genes-in-small-biopsy-specimen-of-lung-cancer
#20
Fumihiro Oshita, Rika Kasajima, Yohei Miyagi
We evaluated multiple oncogenic mutations and fusion genes in small specimen obtained by bronchoscopy. Eight patients with lung cancer were recruited, 3 small cell lung cancer, 3 non-small cell lung cancer, 1 adenocarcinoma and 1 squamous cell carcinoma. A median value of extracted RNA and DNA amounts from specimen was 1573 ng (range 367.5 to 8900) and 6700 ng (range 550 to 68000 ng), respectively. We applied amplicon sequencing panels that cover exon regions of 41 genes related to lung tumorigenesis as well as total 61 major variants of ALK, ROS, RET or NTRK1 fusion transcripts...
July 2016: Journal of Experimental Therapeutics & Oncology
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