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Alk translocation

Jeong-Oh Kim, Jung-Young Shin, Min Young Kim, Kyoung Hwa Son, Chan Kwon Jung, Tae-Jung Kim, Su Young Kim, Jae Kil Park, Sook Whan Sung, Sang Ju Bae, Hyun Jung Min, Jin-Hyoung Kang
BACKGROUND: We screened resected tumor tissues from patients with lung cancer for EGFR mutations, ALK rearrangements, and rearranged during transfection (RET) gene variants (including RET rearrangements and the Kinesin Family Member 5B (KIF5B)-RET fusion gene) using various methods including reverse transcription polymerase chain reaction (RT-PCR), transcript assays, fluorescence in situ hybridization (FISH), and immunohistochemistry (IHC). We also examined the protein expression of associated downstream signaling molecules to assess the effect of these variants on patient outcome...
March 2018: Surgical Oncology
David R Spigel, Craig Reynolds, David Waterhouse, Edward B Garon, Jason Chandler, Sunil Babu, Paul Thurmes, Alexander Spira, Robert Jotte, Jin Zhu, Wen Hong Lin, George Blumenschein
INTRODUCTION: Crizotinib, an anaplastic lymphoma kinase inhibitor, is a first-line treatment for ALK translocation-positive advanced non-small cell lung cancer (NSCLC); however, patients eventually progress. Immunotherapies, including the programmed death-1 inhibitor nivolumab, have resulted in durable responses and long-term overall survival in patients with NSCLC. We hypothesized that combining targeted therapy with immunotherapy could result in more patients with responses and/or more durable responses...
March 5, 2018: Journal of Thoracic Oncology
Cosimo Lobello, Vasilis Bikos, Andrea Janikova, Sarka Pospisilova
Genomic stability is crucial for cell life and transmitting genetic material is one of the primary tasks of the cell. The cell needs to be able to recognize any possible error and quickly repair it, and thus, cells have developed several mechanisms to detect DNA damage and promote repair during evolution. The DNA damage response (DDR) and DNA repair pathways ensure the control of possible errors that could impair the duplication of genetic information and introduce variants in the DNA. Endogenous and exogenous factors compromise genomic stability and cause dysregulation in the DDR and DNA repair pathways...
March 5, 2018: Cancers
B Melosky, N Blais, P Cheema, C Couture, R Juergens, S Kamel-Reid, M-S Tsao, P Wheatley-Price, Z Xu, D N Ionescu
Background: The development and approval of both targeted and immune therapies for patients with advanced non-small cell lung cancer (nsclc) has significantly improved patient survival rates and quality of life. Biomarker testing for patients newly diagnosed with nsclc, as well as for patients progressing after treatment with epidermal growth factor receptor ( EGFR ) inhibitors, is the standard of care in Canada and many parts of the world. Methods: A group of thoracic oncology experts in the field of thoracic oncology met to describe the standard for biomarker testing for lung cancer in the Canadian context, focusing on evidence-based recommendations for standard-of-care testing for EGFR , anaplastic lymphoma kinase ( ALK ), ROS1 , BRAF V600 and programmed death-ligand (PD-L1) at the time of diagnosis of advanced disease and EGFR T790M upon progression...
February 2018: Current Oncology
Mark Kriegsmann, Alexander Harms, Daniel Kazdal, Sebastian Fischer, Albrecht Stenzinger, Jonas Leichsenring, Roland Penzel, Rémi Longuespée, Katharina Kriegsmann, Thomas Muley, Seyer Safi, Arne Warth
In the last decade it became evident that many lung adenocarcinomas (ADC) harbor key genetic alterations such as KRAS, EGFR or BRAF mutations as well as rearrangements of ROS1 or ALK that drive these tumors. In the present study we investigated whether different driver mutations of ADC result in different proliferation rates, which might have clinical impact, including resistance to therapy, recurrence and prognosis. We analyzed the proliferation index (PI) on full slides of surgically resected ADC (n = 230) with known genetic aberrations by means of immunohistochemistry and subsequent digital image analysis and correlated the results with clinicopathological variables including overall (OS) and disease free survival (DFS)...
January 2, 2018: Pathology, Research and Practice
Ling Tan, Yerong Hu, Yongguang Tao, Bin Wang, Jun Xiao, Zhenjie Tang, Ting Lu, Hao Tang
BACKGROUND: To identify whether RET is a potential target for NSCLC treatment, we examined the status of the RET gene in 631 early and mid stage NSCLC cases from south central China. METHODS: RET expression was identified by Western blot. RET-positive expression samples were verified by immunohistochemistry. RET gene mutation, copy number variation, and rearrangement were analyzed by DNA Sanger sequencing, TaqMan copy number assays, and reverse transcription-PCR...
February 23, 2018: Thoracic Cancer
George E Naoum, Michael Morkos, Brian Kim, Waleed Arafat
Thyroid cancer is a frequently encountered endocrine malignancy. Despite the favorable prognosis of this disease, 15-20% of differentiated thyroid cancer (DTC) cases and most anaplastic types, remain resistant to standard treatment options, including radioactive iodine (RAI). In addition, around 30% of medullary thyroid cancer (MTC) cases show resistance after surgery. The evolving understanding of disease-specific molecular therapeutic targets has led to the approval of two targeted therapies (Sorafenib and Lenvatinib) for RAI refractory DTC and another two drugs (Vandetanib and Cabozantinib) for MTC...
February 19, 2018: Molecular Cancer
Q X Gong, H Li, Z H Zhang, Q H Fan
Objective: To study the clinicopathologic features, diagnosis and differential diagnosis of pulmonary microcystic fibromyxoma. Methods: In March 2014, at the First Affiliated Hospital to Nanjing Medical University a 58-year-old female patient of pulmonary microcystic fibromyxoma was collected. The clinicopathologic, immunohistochemical and genetic profile of a case of pulmonary microcystic fibromyxoma were studied, and the relevant literature reviewed. Results: The patient was a 58-year-old female who presented with cough and sputum for 1 month...
February 8, 2018: Zhonghua Bing Li Xue za Zhi Chinese Journal of Pathology
Fei Zhou, Likun Hou, Ting Ding, Quanming Song, Xiaoxia Chen, Chunxia Su, Wei Li, Guanghui Gao, Shengxiang Ren, Fengying Wu, Jiang Fan, Chunyan Wu, Jie Zhang, Caicun Zhou
BACKGROUND: Pulmonary large cell neuroendocrine carcinoma (LCNEC) represents a rare entity in lung cancer with dismal prognosis. In the present study, we investigated whether there are significant differences between central and peripheral tumors of LCNEC, in terms of clinicopathologic features, genomic profiles, and survival. METHODS AND MATERIALS: A total of 126 cases of LCNEC were included. The tumors with invasion of the segmental and/or lobar bronchus were classified as central LCNEC and those without as peripheral LCNEC...
February 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
Yohan Bodokh, Damien Ambrosetti, Valérie Kubiniek, Branwel Tibi, Matthieu Durand, Jean Amiel, Morgane Pertuit, Anne Barlier, Florence Pedeutour
Seven cases of translocation-associated renal cell carcinoma involving ALK (ALK-tRCC) were referenced in the last World Health Organization's classification (2016), in a group of emerging/provisional RCC. The first three cases were pediatric, medullary-based, associated with sickle-cell trait and showed a fusion of ALK with VCL. Thirteen cases have been further described. They displayed clinical, morphological and genomic heterogeneity. Most of them occurred in adults. None of the patients was affected by sickle-cell disease...
February 2018: Cancer Genetics
Joël Bourquin, Ana Milosevic, Daniel Hauser, Roman Lehner, Fabian Blank, Alke Petri-Fink, Barbara Rothen-Rutishauser
Realization of the immense potential of nanomaterials for biomedical applications will require a thorough understanding of how they interact with cells, tissues, and organs. There is evidence that, depending on their physicochemical properties and subsequent interactions, nanomaterials are indeed taken up by cells. However, the subsequent release and/or intracellular degradation of the materials, transfer to other cells, and/or translocation across tissue barriers are still poorly understood. The involvement of these cellular clearance mechanisms strongly influences the long-term fate of used nanomaterials, especially if one also considers repeated exposure...
February 1, 2018: Advanced Materials
Irene Moya-Horno, Santiago Viteri, Niki Karachaliou, Rafael Rosell
Treatment for advanced non-small cell lung cancer (NSCLC) has been significantly improved in recent years with the incorporation of drugs targeting antiangiogenesis and more specifically genomic alterations such as the EGFR mutations and ALK translocations. However, most patients invariably progress and die. The emergence of immune checkpoint inhibitors targeting the pathways involved in tumor-induced immunosuppression have redefined the management of the disease, achieving significant long-lasting responses with manageable safety profiles, regardless of histology...
2018: Therapeutic Advances in Medical Oncology
Nevim Aygun
Neuroblastoma derived from primitive cells of the sympathetic nervous system typically develops in the adrenal medulla or paraspinal ganglia. Neuroblastoma usually occurs sporadically, but familial cases are also observed. ALK and PHOX2B germline mutations can cause hereditary neuroblastoma, while a common genetic variation in chromosome 6p22 is associated to sporadic neuroblastoma. However, the aetiology of sporadic neuroblastoma is not exactly known. This embryonic malignancy generally represents the second most common solid tumour after central nervous system tumours throughout the world in childhood...
January 28, 2018: Current Pediatric Reviews
Ibu Matsuzaki, Hideto Iguchi, Yurina Mikasa, Hiromu Morishita, Katsuya Okuda, Keita Nakaguchi, Yuki Mori, Yoshifumi Iwahashi, Kenji Warigaya, Masakazu Fujimoto, Fumiyoshi Kojima, Shin-Ichi Murata
Identification of fusion genes in cancer is essential for pathological diagnosis and clinical therapy. Although methods for detection of fusion genes, such as fluorescence in situ hybridization (FISH) and real-time polymerase chain reaction (PCR), have been developed in last two decades, these methods are not ideal for detection of these genetic alterations owing to their high cost and time-consuming procedures. In this study, we developed novel application for detection of gene translocations using loop-mediated isothermal amplification (LAMP)...
December 26, 2017: Acta Histochemica et Cytochemica
Brendan C Dickson, David Swanson, George S Charames, Christopher Dm Fletcher, Jason L Hornick
Epithelioid fibrous histiocytoma is a rare and distinctive cutaneous neoplasm. Most cases harbor ALK rearrangement and show ALK overexpression, which distinguish this neoplasm from conventional cutaneous fibrous histiocytoma and variants. SQSTM1 and VCL have previously been shown to partner with ALK in one case each of epithelioid fibrous histiocytoma. The purpose of this study was to examine a large cohort of epithelioid fibrous histiocytomas by next-generation sequencing to characterize the nature and prevalence of ALK fusion partners...
January 12, 2018: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
Qiqi Gao, Honghai Ma, Bo Wang, Yake Yao, Jianya Zhou, Jianying Zhou
Background: The anaplastic lymphoma kinase (ALK) protein has recently become a promising target in the treatment of non-small cell lung carcinomas(NSCLC) patients with ALK translocation because of the high response rates obtained with an ALK inhibitor. ALK translocations are present in approximately 3-5% of NSCLC patients. According to the literature, little information about the relationship of ALK status between the primary tumor and metastatic sites has been reported. We intended to determine whether the ALK translocations of primary lung cancers are consistent with those in corresponding metastatic lymph node tumors...
December 12, 2017: Oncotarget
Ying Dai, Quanxiang Wei, Christian Schwager, Janina Hanne, Cheng Zhou, Klaus Herfarth, Stefan Rieken, Kenneth E Lipson, Jürgen Debus, Amir Abdollahi
BACKGROUND: Patients with Echinoderm microtubule-associated protein-like 4 (EML4)-anaplastic lymphoma kinase (ALK) positive lung cancer are sensitive to ALK-kinase inhibitors. TAE684 is a potent second generation ALK inhibitor that overcomes Crizotinib resistance. Radiotherapy is an integral therapeutic component of locally advanced lung cancer. Therefore, we sought to investigate the effects of combined radiotherapy and ALK-inhibition via TAE684 in ALK-positive vs. wild type lung cancer cells...
January 5, 2018: Radiation Oncology
Tao Fan, Xiu-Li Liu, Jun Zhou, Ying-Jie Song, Hong Yang, Ya-Nan Wei
A patient presenting with concomitant epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocation is very rare. We report a non-small cell lung cancer (NSCLC) patient with concomitant EGFR (exon 19-del) mutation and ALK rearrangement. The positron emission tomography-computed tomography (PET-CT) scan revealed a highly metabolic mass lesion in the left lower lobe, measured 5.0 cm in the largest dimension in the S6 segment. Transbronchial lung biopsy (TBLB) showed the pathological diagnosis of invasive adenocarcinoma...
January 2018: Journal of the College of Physicians and Surgeons—Pakistan: JCPSP
Giulia Gallerani, Claudia Cocchi, Martine Bocchini, Filippo Piccinini, Francesco Fabbri
Circulating tumor cells (CTCs) are associated with poor survival in metastatic cancer. Their identification, phenotyping, and genotyping could lead to a better understanding of tumor heterogeneity and thus facilitate the selection of patients for personalized treatment. However, this is hampered because of the rarity of CTCs. We present an innovative approach for sampling a high volume of the patient blood and obtaining information about presence, phenotype, and gene translocation of CTCs. The method combines immunofluorescence staining and DNA fluorescent-in-situ-hybridization (DNA FISH) and is based on a functionalized medical wire...
December 21, 2017: Journal of Visualized Experiments: JoVE
P B Wagle, N A Jambhekar, R Kumar, K Prabhash, C S Pramesh, S B Desai, V Noronha, G Karimundackal, A Shah, A Joshi, S G Laskar, S Jiwnani, T Pai, J P Agarwal
INTRODUCTION: Testing for echinoderm microtubule-associated protein-like 4 (EML4) anaplastic lymphoma kinase (ALK) translocation by fluorescence in situ hybridization (FISH) is well established whereas the Food and Drug Administration (FDA) ALK immunohistochemical (IHC) test is relatively new. AIMS AND OBJECTIVE: The aim of this study is to compare FDA-approved ALK IHC test (D5F3 clone) with the standard ALK FISH test. MATERIALS AND METHODS: A validation and a test arm with 100 and 200 cases of Formalin-Fixed, Paraffin-embedded blocks of lung adenocarcinoma, respectively, comprised the material...
January 2017: Indian Journal of Cancer
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