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https://www.readbyqxmd.com/read/28101031/alectinib-induced-erythema-multiforme-and-successful-rechallenge-with-alectinib-in-a-patient-with-anaplastic-lymphoma-kinase-rearranged-lung-cancer
#1
Tatsuo Kimura, Junko Sowa-Osako, Toshiyuki Nakai, Ayako Ohyama, Tomoya Kawaguchi, Daisuke Tsuruta, Masahiko Ohsawa, Kazuto Hirata
BACKGROUND: Alectinib is an oral drug developed for the treatment of patients with fusion gene encoding echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK)-rearranged non-small cell lung cancer (NSCLC). Here, we present the case of a patient treated with alectinib who developed a hypersensitivity reaction with successful rechallenge treatment. CASE PRESENTATION: A 39-year-old woman who was a passive smoker was referred to Osaka City University Hospital for the evaluation of a skin event caused by treatment for NSCLC with the fusion gene EML4-ALK...
September 2016: Case Reports in Oncology
https://www.readbyqxmd.com/read/28093881/a-case-of-anaplastic-lymphoma-kinase-alk-positive-ciliated-muconodular-papillary-tumor-cmpt-of-the-lung
#2
Ryo Taguchi, Kayoko Higuchi, Motohiro Sudo, Kenji Misawa, Takashi Miyamoto, Osamu Mishima, Morihisa Kitano, Koji Azuhata, Nobuo Ito
Ciliated muconodular papillary tumor (CMPT) is a rare papillary tumor that arises in the peripheral lung fields and is associated with the proliferation of ciliate d and goblet cells and increased mucin production. We report a case of CMPT involving the rearrangement of the anaplastic lymphoma kinase (ALK) gene. The patient was an 84-year-old Japanese female who had exhibited a small nodular shadow on chest computed tomography during a regular checkup 10 years ago. She underwent a partial resection of segment S10 of the right lung...
January 17, 2017: Pathology International
https://www.readbyqxmd.com/read/28088512/ros1-fusions-rarely-overlap-with-other-oncogenic-drivers-in-non-small-cell-lung-cancer
#3
Jessica J Lin, Lauren L Ritterhouse, Siraj M Ali, Mark Bailey, Alexa B Schrock, Justin F Gainor, Lorin A Ferris, Mari Mino-Kenudson, Vincent A Miller, Anthony J Iafrate, Jochen K Lennerz, Alice T Shaw
INTRODUCTION: Chromosomal rearrangements involving the ROS proto-oncogene 1 receptor tyrosine kinase gene (ROS1) define a distinct molecular subset of non-small cell lung cancer (NSCLC) with sensitivity to ROS1 inhibitors. Recent reports have suggested a significant overlap between ROS1 fusions and other oncogenic driver alterations, including mutations in epidermal growth factor receptor (EGFR) and KRAS proto-oncogene (KRAS). METHODS: We identified patients at our institution with ROS1-rearranged NSCLC who had undergone testing for genetic alterations in additional oncogenes, including EGFR, KRAS, and anaplastic lymphoma kinase (ALK)...
January 11, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28073897/identification-of-alk-ros1-and-ret-fusions-by-a-multiplexed-mrna-based-assay-in-formalin-fixed-paraffin-embedded-samples-from-advanced-non-small-cell-lung-cancer-patients
#4
Noemí Reguart, Cristina Teixidó, Ana Giménez-Capitán, Laia Paré, Patricia Galván, Santiago Viteri, Sonia Rodríguez, Vicente Peg, Erika Aldeguer, Nuria Viñolas, Jordi Remon, Niki Karachaliou, Esther Conde, Fernando Lopez-Rios, Ernest Nadal, Sabine Merkelbach-Bruse, Reinhard Büttner, Rafael Rosell, Miguel A Molina-Vila, Aleix Prat
BACKGROUND: Anaplastic lymphoma receptor tyrosine kinase (ALK), ROS protooncogene 1, receptor tyrosine kinase (ROS1), and ret protooncogene (RET) fusions are present in 5%-7% of patients with advanced non-small-cell lung cancer (NSCLC); their accurate identification is critical to guide targeted therapies. FISH and immunohistochemistry (IHC) are considered the gold standards to determine gene fusions, they have limitations. The nCounter platform is a potentially useful genomic tool for multiplexed detection of gene fusions, but has not been validated in the clinical setting...
January 10, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/28069802/genomic-profiling-of-a-large-set-of-diverse-pediatric-cancers-identifies-known-and-novel-mutations-across-tumor-spectra
#5
Juliann Chmielecki, Mark Bailey, Jie He, Julia Elvin, Jo-Anne Vergilio, Shakti Ramkissoon, James Suh, Garrett M Frampton, James X Sun, Samantha Morley, Daniel Spritz, Siraj Ali, Laurie Gay, Rachel L Erlich, Jeffrey S Ross, Joana Buxhaku, Hilary Davies, Vinny Faso, Alexis Germain, Blair Glanville, Vincent A Miller, Philip J Stephens, Katherine A Janeway, John M Maris, Soheil Meshinchi, Trevor J Pugh, Jack F Shern, Doron Lipson
Pediatric cancers are generally characterized by low mutational burden and few recurrently mutated genes. Recent studies suggest that genomic alterations may help guide treatment decisions and clinical trial selection. Here, we describe genomic profiles from 1,215 pediatric tumors representing sarcomas, extracranial embryonal tumors, brain tumors, hematologic malignancies, carcinomas, and gonadal tumors. Comparable published datasets identified similar frequencies of clinically relevant alterations, validating this dataset as biologically relevant...
January 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28065467/lung-adenocarcinoma-with-muc4-expression-is-associated-with-smoking-status-her2-protein-expression-and-poor-prognosis-clinicopathologic-analysis-of-338-cases
#6
Mariyo Rokutan-Kurata, Akihiko Yoshizawa, Shinji Sumiyoshi, Makoto Sonobe, Toshi Menju, Masanobu Momose, Mizuki Koyama, Shohei Shigeto, Masakazu Fujimoto, Meng Zhang, Satoshi Morita, Hiroshi Date, Hironori Haga
BACKGROUND: MUC4 is a transmembrane glycoprotein that plays a role in the cell growth signaling pathway and has been studied in various organ malignancies. This study aimed to analyze MUC4 expression in resected lung adenocarcinomas (ADCs) to define the clinicopathologic characteristics of MUC4-positive cancers. PATIENTS AND METHODS: Immunohistochemical MUC4 analysis was performed using tissue microarray slides containing 338 lung ADCs. Associations between MUC4 expression and the following clinicopathologic parameters were evaluated: sex; age; smoking status; tumor stage; tumor grade; lymphovascular invasion; pleural invasion; TTF-1 and HNF4α expression; EGFR, KRAS, BRAF, and HER2 mutation status; and ALK and ROS1 fusion status...
December 2, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28065229/detection-of-echinoderm-microtubule-associated-protein-like-4-anaplastic-lymphoma-kinase-fusion-genes-in-non-small-cell-lung-cancer-clinical-samples-by-a-real-time-quantitative-reverse-transcription-polymerase-chain-reaction-method
#7
Jing Zhao, Jin-Yin Zhao, Zhi-Xia Chen, Wei Zhong, Long-Yun Li, Li-Cheng Liu, Xiao-Xu Hu, Wei-Jun Chen, Meng-Zhao Wang
Objective To establish a real-time quantitative reverse transcription polymerase chain reaction assay (qRT-PCR) for the rapid, sensitive, and specific detection of echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) fusion genes in non-small cell lung cancer. Methods The specific primers for the four variants of EML4-ALK fusion genes (V1, V2, V3a, and V3b) and Taqman fluorescence probes for the detection of the target sequences were carefully designed by the Primer Premier 5...
December 20, 2016: Zhongguo Yi Xue Ke Xue Yuan Xue Bao. Acta Academiae Medicinae Sinicae
https://www.readbyqxmd.com/read/28064454/hgf-met-in-cancer-progression-and-biomarker-discovery
#8
REVIEW
Kunio Matsumoto, Masataka Umitsu, Dinuka M De Silva, Arpita Roy, Donald P Bottaro
Signaling driven by hepatocyte growth factor (HGF) and MET receptor facilitates conspicuous biological responses such as epithelial cell migration, 3-D morphogenesis, and survival. The dynamic migration and promotion of cell survival induced by MET activation are bases respectively for invasion-metastasis and resistance against targeted drugs in cancers. Recent studies indicated that MET in tumor-derived exosomes facilitates metastatic niche formation and metastasis in malignant melanoma. In lung cancer, gene amplification-induced MET activation and ligand-dependent MET activation in autocrine/paracrine manner are causes for resistance to EGF receptor tyrosine kinase inhibitors and ALK inhibitors...
January 8, 2017: Cancer Science
https://www.readbyqxmd.com/read/28063177/comparable-clinical-outcomes-in-patients-with-her2-mutant-and-egfr-mutant-lung-adenocarcinomas
#9
Chien-Hung Gow, Hou-Tai Chang, Chor-Kuan Lim, Chao-Yu Liu, Jin-Shing Chen, Jin-Yuan Shih
HER2 is a major proliferative driver in lung cancer. HER2 gene aberrations impact the prognosis of lung adenocarcinoma (ADC). A one-step reverse transcription-polymerase chain reaction was performed using RNA samples from 888 Asian lung cancer patients to detect HER2, EGFR, KRAS, ALK, and ROS1 mutations. The demographic data and treatment outcomes of HER2 mutation-positive lung ADC patients were analyzed and compared to those with HER2 mutation-negative tumors. HER2 mutation was identified in 40 (4.5%) lung ADC patients...
January 7, 2017: Genes, Chromosomes & Cancer
https://www.readbyqxmd.com/read/28050598/alk-a-tyrosine-kinase-target-for-cancer-therapy
#10
REVIEW
Vijaykumar R Holla, Yasir Y Elamin, Ann Marie Bailey, Amber M Johnson, Beate C Litzenburger, Yekaterina B Khotskaya, Nora S Sanchez, Jia Zeng, Md Abu Shufean, Kenna R Shaw, John Mendelsohn, Gordon B Mills, Funda Meric-Bernstam, George R Simon
The anaplastic lymphoma kinase (ALK) gene plays an important physiologic role in the development of the brain and can be oncogenically altered in several malignancies, including non-small-cell lung cancer (NSCLC) and anaplastic large cell lymphomas (ALCL). Most prevalent ALK alterations are chromosomal rearrangements resulting in fusion genes, as seen in ALCL and NSCLC. In other tumors, ALK copy-number gains and activating ALK mutations have been described. Dramatic and often prolonged responses are seen in patients with ALK alterations when treated with ALK inhibitors...
January 2017: Cold Spring Harbor Molecular Case Studies
https://www.readbyqxmd.com/read/28050384/inflammatory-myofibroblastic-tumor-of-the-kidney-a-rare-renal-tumor
#11
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/28038678/human-splicing-diversity-and-the-extent-of-unannotated-splice-junctions-across-human-rna-seq-samples-on-the-sequence-read-archive
#12
Abhinav Nellore, Andrew E Jaffe, Jean-Philippe Fortin, José Alquicira-Hernández, Leonardo Collado-Torres, Siruo Wang, Robert A Phillips Iii, Nishika Karbhari, Kasper D Hansen, Ben Langmead, Jeffrey T Leek
BACKGROUND: Gene annotations, such as those in GENCODE, are derived primarily from alignments of spliced cDNA sequences and protein sequences. The impact of RNA-seq data on annotation has been confined to major projects like ENCODE and Illumina Body Map 2.0. RESULTS: We aligned 21,504 Illumina-sequenced human RNA-seq samples from the Sequence Read Archive (SRA) to the human genome and compared detected exon-exon junctions with junctions in several recent gene annotations...
December 30, 2016: Genome Biology
https://www.readbyqxmd.com/read/28031835/pulmonary-lymphoepithelioma-like-carcinoma-with-echinoderm-microtubule-associated-protein-like-4-anaplastic-lymphoma-kinase-eml4-alk-fusion-gene
#13
Naoko Ose, Teruka Kawai, Daisuke Ishida, Yuko Kobori, Yukiyasu Takeuchi, Hidetoshi Senba
A pulmonary lymphoepithelioma-like carcinoma (PLELC) is similar to a lymphoepithelioma, a subtype of nasopharyngeal carcinoma and commonly associated with Epstein-Barr virus infection which is a rare tumour and classified in the group of "other and unclassified carcinoma" in the latest 2015 World Health Organization (WHO) classification. Some reports of lymphoepithelioma-like carcinoma (LELC) have noted an epidermal growth factor receptor (EGFR) mutation, whereas none have noted a mutation of the echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) fusion gene...
November 2016: Respirology Case Reports
https://www.readbyqxmd.com/read/28027327/mutational-profile-of-metastatic-breast-cancers-a-retrospective-analysis
#14
Celine Lefebvre, Thomas Bachelot, Thomas Filleron, Marion Pedrero, Mario Campone, Jean-Charles Soria, Christophe Massard, Christelle Lévy, Monica Arnedos, Magali Lacroix-Triki, Julie Garrabey, Yannick Boursin, Marc Deloger, Yu Fu, Frédéric Commo, Véronique Scott, Ludovic Lacroix, Maria Vittoria Dieci, Maud Kamal, Véronique Diéras, Anthony Gonçalves, Jean-Marc Ferrerro, Gilles Romieu, Laurence Vanlemmens, Marie-Ange Mouret Reynier, Jean-Christophe Théry, Fanny Le Du, Séverine Guiu, Florence Dalenc, Gilles Clapisson, Hervé Bonnefoi, Marta Jimenez, Christophe Le Tourneau, Fabrice André
BACKGROUND: Major advances have been achieved in the characterization of early breast cancer (eBC) genomic profiles. Metastatic breast cancer (mBC) is associated with poor outcomes, yet limited information is available on the genomic profile of this disease. This study aims to decipher mutational profiles of mBC using next-generation sequencing. METHODS AND FINDINGS: Whole-exome sequencing was performed on 216 tumor-blood pairs from mBC patients who underwent a biopsy in the context of the SAFIR01, SAFIR02, SHIVA, or Molecular Screening for Cancer Treatment Optimization (MOSCATO) prospective trials...
December 2016: PLoS Medicine
https://www.readbyqxmd.com/read/28024928/molecular-profiling-and-survival-of-completely-resected-primary-pulmonary-neuroendocrine-carcinoma
#15
Guangyuan Lou, Xinmin Yu, Zhengbo Song
BACKGROUND: Currently, molecular profiles and prognosis of primary pulmonary neuroendocrine carcinoma (PNC) are poorly elucidated. The present study was designed to evaluate genomic abnormalities and survival in patients with primary PNC. METHODS: Completely resected PNC samples were collected from Zhejiang Cancer Hospital during the period of 2008 to 2015. Nine driver genes, including 6 mutations (EGFR, KRAS, NRAS, PIK3CA, BRAF, and HER2) and 3 fusions (ALK, ROS1, and RET), were evaluated by reverse transcription-polymerase chain reaction (RT-PCR)...
December 2, 2016: Clinical Lung Cancer
https://www.readbyqxmd.com/read/28024701/a-comprehensive-analysis-of-clinical-outcomes-in-lung-cancer-patients-harboring-a-met-exon-14-skipping-mutation-compared-to-other-driver-mutations-in-an-east-asian-population
#16
Chien-Hung Gow, Min-Shu Hsieh, Shang-Gin Wu, Jin-Yuan Shih
INTRODUCTION: Recurrent somatic splice-site alterations at MET exon 14 (MET(Δ14)), which result in exon skipping and MET proto-oncogene, receptor tyrosine kinase (MET) activation, have been characterised. However, their demographic features and clinical outcomes in East Asian lung cancer patients have yet to be determined. METHODS: A one-step reverse transcription-polymerase chain reaction (RT-PCR), using RNA samples from 850 East Asian lung cancer patients, was performed in order to detect MET(Δ14) and five other major driver mutations, including those in the EGFR, KRAS, ALK, HER2, and ROS1 genes...
January 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28018791/successful-ceritinib-treatment-in-a-man-with-mpe-and-an-alk-fusion-gene-mutation-after-multiple-treatments
#17
Hangping Wei, Fangming Du, Yifang Lu, Juan Wei, Xiaofang Dong
INTRODUCTION: Ceritinib is a second-generation anaplastic lymphoma kinase (ALK) inhibitor. It inhibits two of the most common ALK-mutants that confer resistance to crizotinib. Ceritinib was approved by Food and Drug Administration in April 2014. However, the efficacy of ceritinib in Asian patients have not been widely studied. Decrease of malignant pleural effusion (MPE) has been rarely reported after treatment with ceritinib. CASE DESCRIPTION: A 50-year old man diagnosed with stage IV lung adenocarcinoma presented with MPE and an ALK fusion gene mutation...
2016: SpringerPlus
https://www.readbyqxmd.com/read/28013235/kinase-impact-assessment-in-the-landscape-of-fusion-genes-that-retain-kinase-domains-a-pan-cancer-study
#18
Pora Kim, Peilin Jia, Zhongming Zhao
Assessing the impact of kinase in gene fusion is essential for both identifying driver fusion genes (FGs) and developing molecular targeted therapies. Kinase domain retention is a crucial factor in kinase fusion genes (KFGs), but such a systematic investigation has not been done yet. To this end, we analyzed kinase domain retention (KDR) status in chimeric protein sequences of 914 KFGs covering 312 kinases across 13 major cancer types. Based on 171 kinase domain-retained KFGs including 101 kinases, we studied their recurrence, kinase groups, fusion partners, exon-based expression depth, short DNA motifs around the break points and networks...
December 24, 2016: Briefings in Bioinformatics
https://www.readbyqxmd.com/read/28009326/alk-gene-copy-number-in-lung-cancer-unspecific-polyploidy-versus-specific-amplification-visible-as-double-minutes
#19
Anna Caliò, Emilio Bria, Sara Pilotto, Eliana Gilioli, Alessia Nottegar, Albino Eccher, Luca Cima, Antonio Santo, Serena Pedron, Giona Turri, Sakari Knuutila, Marco Chilosi, Francesca Vanzo, Giuseppe Bogina, Alberto Terzi, Giampaolo Tortora, Aldo Scarpa, Massimo Loda, Guido Martignoni, Matteo Brunelli
BACKGROUND: Gains of a gene due to DNA polyploidy versus amplification of the specific locus are distinct molecular alterations in tumors. OBJECTIVE: We quantified copy number gains of ALK gene due to unspecific polyploidy versus amplifications of the specific locus in a series of non-small cell lung cancers. METHODS: The locus specific ALK copy (LSI) number status was evaluated in 205 cases by FISH. Ratio LSI ALK copy number corrected for control probes CEP2, CEP3 and CEP17 (CEPs) was scored...
December 16, 2016: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/28003677/two-relapsed-stage-iii-childhood-anaplastic-large-cell-lymphoma-patients-with-npm-alk-fusion-in-bone-marrow-from-initial-diagnosis
#20
Yui Kanazawa, Yuka Yamashita, Mitsuhiro Fujiwara, Michiko Muraoka, Kana Washio, Kiichiro Kanamitsu, Hisashi Ishida, Takae Nakano, Miho Yamada, Keizo Horibe, Takehiro Tanaka, Tadashi Yoshino, Akira Shimada
Childhood anaplastic large cell lymphoma (ALCL) accounts for approx. 10-30% of cases of non-Hodgkin lymphoma, and the ALCL99 study reported 60-75 disease-free survival; however, a relatively high relapse rate was observed (25-30% ). We report 2 patients with Stage III ALCL who relapsed 6-18 months after the end of ALCL99 chemotherapy. A retrospective molecular analysis identified the nucleophosmin (NPM)-anaplastic lymphoma kinase (ALK) fusion gene in the first diagnostic bone marrow samples taken from both patients...
December 2016: Acta Medica Okayama
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