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https://www.readbyqxmd.com/read/28931104/-molecular-diagnostics-of-alk-positive-lung-cancer
#1
József Tímár, Gábor Lotz, Erzsébet Rásó, Judit Moldvay
ALK translocation is the 3rd most frequent genetic aberration in lung adenocarcinoma, and several inhibitors are now clinically available in first and second line settings. Accordingly, molecular diagnostics of ALK-positive lung cancer is very important and can be done with the rational combination of several methods. All international recommendations suggest that, except for cytological samples, screening technology for ALK-positive tumors is immunohistochemistry using a validated test. It is highly recommended that in case of ALK protein positive samples gene translocation must be confirmed by fluorescent in situ hybridization (FISH)...
September 20, 2017: Magyar Onkologia
https://www.readbyqxmd.com/read/28930717/inhibition-of-erythrocyte-cell-membrane-scrambling-by-asp3026
#2
Abdulla Al Mamun Bhuyan, Rosi Bissinger, Hang Cao, Florian Lang
BACKGROUND/AIMS: The anaplastic lymphoma kinase (ALK) inhibitor ASP3026 is in clinical development for the treatment of ALK expressing non-small cell lung carcinoma (NSCLC). ASP3026 is in part effective by inducing apoptosis of tumor cells. Erythrocytes lack mitochondria and nuclei, key organelles in the execution of apoptosis, but are nevertheless able to enter suicidal death or eryptosis, which is characterized by cell membrane scrambling with phosphatidylserine translocation to the cell surface and by cell shrinkage...
September 20, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28895885/anaplastic-lymphoma-kinase-in-cutaneous-malignancies
#3
REVIEW
Severine Cao, Vinod E Nambudiri
Anaplastic lymphoma kinase (ALK) is a receptor tyrosine kinase that has been implicated in the pathogenesis of a variety of neoplasms. As suggested by its name, ALK was first described as part of a translocation product in cases of anaplastic large-cell lymphoma, with other genetic and cytogenetic ALK mutations subsequently coming to attention in the development of many other hematologic and solid organ malignancies. ALK has now been shown to play a role in the pathogenesis of several cutaneous malignancies, including secondary cutaneous systemic anaplastic large-cell lymphoma (ALCL) and primary cutaneous ALCL, melanoma, spitzoid tumors, epithelioid fibrous histiocytoma, Merkel cell carcinoma, and basal cell carcinoma...
September 12, 2017: Cancers
https://www.readbyqxmd.com/read/28887531/homogeneity-and-high-concordance-of-alk-translocation-in-primary-lung-adenocarcinoma-and-paired-lymph-node-metastasis
#4
Wei Ma, Lei Guo, Ling Shan, Xiuyun Liu, Ning Lyu, Jianming Ying
Translocation of anaplastic lymphoma kinase (ALK) gene is an important determinator for the response to ALK tyrosine kinase inhibitor (TKI) in non-small-cell lung cancer (NSCLC) patients. The existence of genetic heterogeneity will affect the results of molecular testing, especially in biopsy samples from primary or metastatic sites of patients with advanced stage NSCLC. We intended to explore the heterogeneity of ALK gene translocation in excision specimens and to examine the existence of discordance of ALK status between primary tumours and corresponding lymph node metastases...
September 8, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28861332/eml4-alk-positive-lung-adenocarcinoma-presenting-an-unusual-metastatic-pattern-in-a-29-year-old-woman-who-is-alive-and-well%C3%A2-in%C3%A2-her-third-year-follow-up-a-case-report
#5
Fatma Tokat, Handan Zeren, Pinar Barut, Sualp Tansan, Umit Ince
Non-small cell lung cancer (NSCLC) is a frequent tumor entity with high mortality. Although several newly discovered chromosomal translocations and mutations opened new horizons for targeted therapy, literature still lacks large series of NSCLC with chromosomal abberations and their correlations with histological and clinical features. We present a case of echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase (EML4-ALK) translocation positive adenocarcinoma of the lung with an unusual metastatic pattern in a 29-year-old young woman...
2017: Respiratory Medicine Case Reports
https://www.readbyqxmd.com/read/28838394/molecular-profiling-in-italian-patients-with-advanced-non-small-cell-lung-cancer-an-observational-prospective-study
#6
Elisa Gobbini, Domenico Galetta, Marcello Tiseo, Paolo Graziano, Antonio Rossi, Emilio Bria, Massimo Di Maio, Giulio Rossi, Vanesa Gregorc, Ferdinando Riccardi, Vieri Scotti, Anna Ceribelli, Lucio Buffoni, Angelo Delmonte, Tindara Franchina, Maria Rita Migliorino, Diego Cortinovis, Salvatore Pisconti, Paola Bordi, Annamaria Catino, Evaristo Maiello, Francesca Arizio, Silvia Novello
OBJECTIVES: Molecular profiling of advanced non-small-cell lung cancer (NSCLC) is recommended according to European and Italian guidelines. However, molecular routine assessment remains still heterogeneous. This observational study aimed to take a picture of the real clinical practice in molecular testing and therapeutic choices in advanced Italian NSCLCs. MATERIALS AND METHODS: This study prospectively enrolled newly diagnosed advanced or recurrent NSCLCs referred to 38 Italian centres, from November 2014 to November 2015...
September 2017: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/28802494/toward-a-molecular-genetic-classification-of-spitzoid-neoplasms
#7
REVIEW
Michael T Tetzlaff, Alexandre Reuben, Steven D Billings, Victor G Prieto, Jonathan L Curry
The histopathologic spectrum of Spitzoid neoplasms includes Spitz nevi, atypical Spitz tumors, and Spitzoid melanomas. Advances in molecular genetics have evolved to the point that Spitzoid lesions can now be reasonably classified according to their distinctive molecular-genetic alterations: Spitzoid lesions with (1) 11p amplification and/or HRAS mutations; (2) isolated loss of 6q23 by fluorescence in situ hybridization (FISH); (3) homozygous deletion of 9p21 by FISH; (4) BAP1 loss and BRAFV600 E mutation; (5) translocations involving any of a number of different oncogenic kinase drivers, including ROS1, ALK, NTRK1, NTRK3, MET, BRAF, and RET; and (6) TERT promoter mutations...
September 2017: Clinics in Laboratory Medicine
https://www.readbyqxmd.com/read/28794371/successful-treatment-with-alectinib-for-choroidal-metastasis-in-anaplastic-lymphoma-kinase-rearranged-non-small-cell-lung-cancer
#8
Tomoko Funazo, Kyohei Morita, Naoya Ikegami, Chisato Konishi, Satoshi Nakao, Ryo Ariyasu, Masato Taki, Kazuhiko Nakagawa, Moon Hee Hwang, Chie Yoshimura, Toshiaki Wakayama, Yasuo Nishizaka
Choroidal metastasis is rare in cancer patients and it may cause visual disturbances that reduce their quality of life. In non-small cell lung cancer (NSCLC), targeted therapy against actionable driver mutations has gradually replaced radiotherapy as the treatment of choice for choroidal metastasis. Recently, there have been several case reports of choroidal metastasis in patients with anaplastic lymphoma kinase (ALK)-rearranged NSCLC. We herein report the case of a 40-year-old Japanese woman diagnosed with choroidal metastasis of an ALK-rearranged NSCLC who received alectinib as the first-line chemotherapy...
August 10, 2017: Internal Medicine
https://www.readbyqxmd.com/read/28763691/treatment-of-elderly-patients-or-patients-who-are-performance-status-2-ps2-with-advanced-non-small-cell-lung-cancer-without-epidermal-growth-factor-receptor-egfr-mutations-and-anaplastic-lymphoma-kinase-alk-translocations-still-a-daily-challenge
#9
REVIEW
Chunxia Su, Fei Zhou, Jiqiao Shen, Jing Zhao, Mary O'Brien
Cytotoxic chemotherapy remains the core treatment strategy for patients with advanced non-small cell lung cancer (NSCLC) with tumours that do not have actionable molecular alterations, such as epidermal growth factor receptor (EGFR)-sensitising mutations, anaplastic lymphoma kinase (ALK) translocations or ROS1 translocations. Age and performance status (PS) are two pivotal factors to guide treatment decisions regarding the use of chemotherapy in lung cancer patients. Lung cancer is predominantly a disease of the elderly, with more than two-thirds of patients aged ≥65 years, the current definition of 'elderly'...
September 2017: European Journal of Cancer
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
#10
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/28756651/relationship-between-driver-gene-mutations-their-relative-protein-expressions-and-survival-in-non-small-cell-lung-carcinoma-in-macao
#11
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
#12
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/28740693/disease-flare-after-discontinuing-gefitinib-in-a-patient-with-lung-adenocarcinoma-and-concomitant-epithelial-growth-factor-receptor-mutation-and-anaplastic-lymphoma-kinase-translocation
#13
Eun Hye Park, Hwa Young Lee, Jin Woo Kim, Chang Dong Yeo
We report on a patient with lung adenocarcinoma and a concomitant epithelial growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocation who developed a disease flare after discontinuing gefitinib. A 63-year-old woman with lung adenocarcinoma and a concomitant activating EGFR mutation and ALK translocation was treated with first-line gefitinib. After 4 months, she discontinued the gefitinib due to disease progression. She was admitted to the emergency room complaining of severe dyspnea and back pain 22 days after discontinuing gefitinib...
June 2017: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28735509/diagnostic-utility-of-automated-surefish-dako-omnis-in-the-diagnosis-of-musculoskeletal-translocation-related-sarcomas
#14
Shintaro Sugita, Tomoyuki Aoyama, Yoshimasa Ito, Hiroko Asanuma, Taro Sugawara, Keiko Segawa, Yumika Ito, Noriaki Kikuchi, Mitsuhiro Tsujiwaki, Hiromi Fujita, Yusuke Ono, Tadashi Hasegawa
Fluorescence in situ hybridization (FISH) is an essential tool for genetic diagnosis in daily pathological work. Almost full automation of FISH can be achieved with the recently released automated SureFISH platform (Dako Omnis, Agilent Technologies, Santa Clara, CA, USA). Its utility has been reported in HER2 amplification of breast and gastric carcinoma and ALK-rearranged lung cancer. Here, we examined the utility of automated SureFISH for the identification of rearrangement signals in translocation-related sarcomas (TRSs), including 11 EWSR1-rearranged and 10 synovial sarcoma cases, compared with non-automated conventional FISH using the same specimens...
July 22, 2017: Pathology International
https://www.readbyqxmd.com/read/28731868/inflammatory-myofibroblastic-tumors-of-the-female-genital-tract-are-under-recognized-a-low-threshold-for-alk-immunohistochemistry-is-required
#15
Justine L Pickett, Angela Chou, Juliana A Andrici, Adele Clarkson, Loretta Sioson, Amy Sheen, Jessica Reagh, Fedaa Najdawi, Yoomee Kim, Denise Riley, Jayne Maidens, David Nevell, Kirsten McIlroy, Susan Valmadre, Greg Gard, Russell Hogg, John Turchini, Gregory Robertson, Michael Friedlander, Anthony J Gill
Inflammatory myofibroblastic tumor (IMT) of the female genital tract is under-recognized. We investigated the prevalence of ALK-positive IMT in lesions previously diagnosed as gynecologic smooth muscle tumors. Immunohistochemistry (IHC) for ALK was performed on tissue microarrays of unselected tumors resected from 2009 to 2013. Three of 1176 (0.26%) "leiomyomas" and 1 of 44 (2.3%) "leiomyosarcomas" were ALK IHC positive, confirmed translocated by fluorescence in situ hybridization (FISH) and therefore more appropriately classified as IMT...
October 2017: American Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28721071/adverse-renal-effects-of-anaplastic-lymphoma-kinase-inhibitors-and-the-response-to-alectinib-of-an-alk-lung-cancer-patient-with-renal-dysfunction
#16
Midori Shimada, Minoru Fukuda, Masaaki Fukuda, Takeshi Kitazaki, Kohji Hashiguchi, Takaya Ikeda, Hiroyuki Yamaguchi, Katsumi Nakatomi, Kazuto Ashizawa, Hiroshi Mukae
A 62-year-old female patient with renal dysfunction and pulmonary adenocarcinoma developed postoperative recurrence and received carboplatin/pemetrexed and maintenance pemetrexed. As an anaplastic lymphoma kinase (ALK) gene translocation was identified, the therapy was changed to crizotinib. However, the patient's blood creatinine level increased, and her physical status worsened. Alectinib also induced exacerbation of renal dysfunction but was controlled by dose reduction of 140 mg twice daily for 2 weeks treatment and 2 weeks break were repeated, and exhibited a partial response for 16 months...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28696381/cost-saving-opportunities-in-nsclc-therapy-by-optimized-diagnostics
#17
Ilija Nenadić, Jeanine Staber, Susanne Dreier, Guus Simons, Verena Schildgen, Michael Brockmann, Oliver Schildgen
With an incidence of 68 new cases per 100,000 people per year, an estimated total number of up to 350,000 new non-small-cell lung cancer (NSCLC) cases are diagnosed each year in the European Union. Up to 10% of NSCLC patients are eligible for therapy with novel ALK (anaplastic lymphoma kinase) inhibitors, as they have been diagnosed with a mutation in the gene coding for ALK. The ALK inhibitor therapy costs add up to approx. 9,000 € per patient per month, with treatment durations of up to one year. Recent studies have shown that up to 10% of ALK cases are misdiagnosed by nearly 40% of pathologic investigations...
July 11, 2017: Cancers
https://www.readbyqxmd.com/read/28693749/primary-gastrointestinal-anaplastic-large-cell-lymphoma
#18
Yi-Ying Lee, Katsuyoshi Takata, Ren-Ching Wang, Sheau-Fang Yang, Shih-Sung Chuang
Primary gastrointestinal anaplastic large cell lymphoma (GI-ALCL) is rare. We report eight new cases. The median age was 61.5 years (range 10-88), most frequently involving the stomach (n = 3) and small intestine (n = 4). The neoplastic hallmark cells in all cases expressed CD30. Anaplastic lymphoma kinase (ALK) protein was expressed in two cases (25%). By in situ hybridisation, all cases were negative for Epstein-Barr virus and for DUSP22/IRF4 gene translocation. At a median follow-up time of 37.5 months, four patients died of disease, one was alive with disease, and three were disease-free...
August 2017: Pathology
https://www.readbyqxmd.com/read/28665006/partial-deletion-of-the-alk-gene-in-alk-positive-anaplastic-large-cell-lymphoma
#19
Suguru Fukuhara, Junko Nomoto, Sung-Won Kim, Hirokazu Taniguchi, Akiko Miyagi Maeshima, Kensei Tobinai, Yukio Kobayashi
Anaplastic lymphoma kinase (ALK) protein is an orphan receptor tyrosine kinase that is constitutively activated by aberrant translocations of the ALK gene in anaplastic large cell lymphoma, ALK-positive and several other cancers. Additionally, aberrant mutation and amplification of the ALK gene, resulting in ALK kinase activation, were detected mainly in neuroblastoma. Recently, truncated ALK protein was also reported in neuroblastoma. Here, we describe a novel truncated form of the ALK transcript with in-frame skipping through exons 2 to 17 (ALKΔ2-17) in anaplastic large cell lymphoma, ALK-positive...
June 30, 2017: Hematological Oncology
https://www.readbyqxmd.com/read/28656214/her2-regulates-cancer-stem-like-cell-phenotype-in-alk-translocated-nsclc
#20
Tiia Honkanen, Emmi Wilenius, Peppi Koivunen, Jussi P Koivunen
We have previously shown that cancer stem-like cells (CSLCs) can mediate therapy resistance in ALK translocated lung cancers. HER2 has been linked to CSLCs in breast cancers and, therefore, we wanted to assess whether HER2 has a role in CSLCs in ALK translocated cancers. ALK translocated cell lines, H3122 and H2228, with variable sensitivity to ALK inhibition were used in the study. HER2 overexpression or knockdown was induced by retro- or lentiviral infections and cells were treated with pharmacological agents targeting HER2 and ALK signaling...
June 21, 2017: International Journal of Oncology
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