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https://www.readbyqxmd.com/read/29048432/silencing-fli-or-targeting-cd13-anpep-lead-to-dephosphorylation-of-epha2-a-mediator-of-braf-inhibitor-resistance-and-induce-growth-arrest-or-apoptosis-in-melanoma-cells
#1
Alireza Azimi, Rainer Tuominen, Fernanda Costa Svedman, Stefano Caramuta, Maria Pernemalm, Marianne Frostvik Stolt, Lena Kanter, Pedram Kharaziha, Janne Lehtiö, Carolina Hertzman Johansson, Veronica Höiom, Johan Hansson, Suzanne Egyhazi Brage
A majority of patients with BRAF-mutated metastatic melanoma respond to therapy with BRAF inhibitors (BRAFi), but relapses are common owing to acquired resistance. To unravel BRAFi resistance mechanisms we have performed gene expression and mass spectrometry based proteome profiling of the sensitive parental A375 BRAF V600E-mutated human melanoma cell line and of daughter cell lines with induced BRAFi resistance. Increased expression of two novel resistance candidates, aminopeptidase-N (CD13/ANPEP) and ETS transcription factor FLI1 was observed in the BRAFi-resistant daughter cell lines...
August 31, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29044660/real-world-treatment-patterns-and-outcomes-among-metastatic-cutaneous-melanoma-patients-treated-with-ipilimumab
#2
P M Mohr, P A Ascierto, A A Arance, G M McArthur, A H Hernaez, P K Kaskel, R S Shinde, K S Stevinson
BACKGROUND: There is a scarcity of real-world data on treatment patterns and outcomes among advanced melanoma patients treated with immunotherapies including ipilimumab, an anti-CTLA-4 antibody approved since 2011. OBJECTIVE: To evaluate ipilimumab and post-ipilimumab treatment patterns and outcomes among patients with advanced melanoma in Australia, Germany, Italy and Spain following regulatory approval. METHODS: Retrospective multicentre, multinational, observational chart review study...
October 17, 2017: Journal of the European Academy of Dermatology and Venereology: JEADV
https://www.readbyqxmd.com/read/29039585/identification-of-genome-variations-in-patients-with-lung-adenocarcinoma-using-whole-genome-re%C3%A2-sequencing
#3
Guiyuan Li, Yunqing Mei, Fan Yang, Shengming Yi, Lemin Wang
Lung adenocarcinoma is one of the types of non‑small cell lung carcinoma, which tends to be treated with surgical therapy rather than radiation therapy. It occurs in smokers and non‑smokers, and is the most common form of lung cancer among non‑smokers and women. Gene rearrangements, including ALK, ROS1 and RET, and gene mutations, including epidermal growth factor receptor (EGFR), HER2, Kristen rat sarcoma viral oncogene homolog, BRAF, phosphoinositide‑3‑kinase, catalytic, α polypeptide and MET, have been identified in lung adenocarcinoma, which enable targeted therapy in lung adenocarcinoma, for example erlotinib, gefitinib and afatinib, which are EGFR inhibitors...
October 17, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29037127/role-of-molecular-markers-to-predict-distant-metastasis-in-papillary-thyroid-carcinoma-promising-value-of-tert-promoter-mutations-and-insignificant-role-of-braf-mutations-a-meta-analysis
#4
Huy Gia Vuong, Ahmed Ma Altibi, Uyen Np Duong, Hanh Tt Ngo, Thong Quang Pham, Hung Minh Tran, Naoki Oishi, Kunio Mochizuki, Tadao Nakazawa, Lewis Hassell, Ryohei Katoh, Tetsuo Kondo
The presence of distant metastasis is associated with an adverse outcome in papillary thyroid cancer. We performed a meta-analysis to investigate the role of molecular markers as predictors for distant metastasis in papillary thyroid cancer. Four electronic databases including PubMed, Web of Science, Scopus, and Virtual Health Library were searched, and odds ratio and its 95% confidence interval concerning the association of BRAF, RAS, and TERT promoter mutations and RET/PTC rearrangements with distant metastasis were calculated using random-effects model...
October 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/29035465/enhanced-specificity-of-braf-v600e-genotyping-using-wild-type-blocker-coupled-with-internal-competitive-reference-in-a-single-tube
#5
Jia Peng, Kun Wei, Shu Yu, Xiang Yang, Xiang Zhao, Yu Liu, Xiao-Yan Zhu, Na Zhao, Qing Huang, Wei-Ling Fu
BACKGROUND: Mutations in the BRAF gene have been strongly associated with failure in cancer treatment using epidermal growth factor receptor (EGFR) antibodies. To better diagnose and assess the prognosis of cancer patients, mutation screening of the BRAFV600E gene should be performed prior to clinical anti-tumor drug therapy to avoid ineffective treatment. METHODS: In our previous study, we developed a real-time wild-type blocking PCR (WTB-PCR), which can amplify the mutant allele at high efficiency while simultaneously inhibiting the amplification of wild-type alleles...
October 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/29023643/improved-survival-of-patients-with-melanoma-brain-metastases-in-the-era-of-targeted-braf-and-immune-checkpoint-therapies
#6
Sarah Sloot, Yian A Chen, Xiuhua Zhao, Jamie L Weber, Jacob J Benedict, James J Mulé, Keiran S Smalley, Jeffrey S Weber, Jonathan S Zager, Peter A Forsyth, Vernon K Sondak, Geoffrey T Gibney
BACKGROUND: The development of brain metastases is common for systemic treatment failure in patients with melanoma and has been associated with a poor prognosis. Recent advances with BRAF and immune checkpoint therapies have led to improved patient survival. Herein, the authors evaluated the risk of de novo brain metastases and survival among patients with melanoma brain metastases (MBM) since the introduction of more effective therapies. METHODS: Patients with unresectable AJCC stage III/IV melanoma who received first-line systemic therapy at Moffitt Cancer Center between 2000 and 2012 were identified...
October 12, 2017: Cancer
https://www.readbyqxmd.com/read/29017314/thyroid-fine-needle-aspiration-cytology-practice-in-korea
#7
Yoon Jin Cha, Ju Yeon Pyo, Soon Won Hong, Jae Yeon Seok, Kyung-Ju Kim, Jee-Young Han, Jeong Mo Bae, Hyeong Ju Kwon, Yeejeong Kim, KyuengWhan Min, Soonae Oak, Sunhee Chang
We reviewed the current status of thyroid fine needle aspiration cytology (FNAC) in Korea. Thyroid aspiration biopsy was first introduced in Korea in 1977. Currently, radiologists aspirate the thyroid nodule under the guidance of ultrasonography, and cytologic interpretation is only legally approved when a cytopathologist makes the diagnosis. In 2008, eight thyroid-related societies came together to form the Korean Thyroid Association. The Korean Society for Cytopathology and the endocrine pathology study group of the Korean Society for Pathologist have been updating the cytologic diagnostic guidelines...
October 11, 2017: Journal of Pathology and Translational Medicine
https://www.readbyqxmd.com/read/28994108/value-of-a-molecular-screening-program-to-support-clinical-trial-enrollment-in-asian-cancer-patients-the-integrated-molecular-analysis-of-cancer-imac-study
#8
Valerie Heong, Nicholas L Syn, Xiao Wen Lee, Nur Sabrina Sapari, Xue Qing Koh, Zul Fazreen Adam Isa, Joey Sy Lim, Diana Lim, Brendan Pang, Yee Liang Thian, Lai Kuan Ng, Andrea L Wong, Ross Andrew Soo, Wei Peng Yong, Cheng Ean Chee, Soo-Chin Lee, Boon-Cher Goh, Richie Soong, David S P Tan
The value of precision oncology initiatives in Asian contexts remains unresolved. Here we review the institutional implementation of prospective molecular screening to facilitate accrual of patients into biomarker-driven clinical trials, and to explore the mutational landscape of advanced tumors occurring in a prospective cohort of Asian patients (n = 396) with diverse cancer types. Next-generation sequencing (NGS) and routine clinicopathological assays such as immunohistochemistry, copy number analysis, and in situ hybridization tests were performed on tumor samples...
October 9, 2017: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/28989040/molecular-adequacy-of-image-guided-rebiopsies-for-molecular-retesting-in-advanced-non-small-cell-lung-cancer-a-single-centre-experience
#9
Nadza Tokaca, Sarah Barth, Mary O'Brien, Jaishree Bhosle, Nicos Fotiadis, Andrew Wotherspoon, Lisa Thompson, Sanjay Popat
INTRODUCTION: In the era of biomarker-driven systemic therapy for advanced non-small cell lung cancer (NSCLC), the role of routine repeated biopsies for decision-making, outside EGFR mutant disease, remains unproven. We report our centre's experience of safety and adequacy for molecular retesting of tumour material obtained from image-guided lung rebiopsies in NSCLC. METHODS: We performed a retrospective case-note analysis of patients undergoing image-guided lung rebiopsies at a single cancer centre between 2011-14...
October 5, 2017: Journal of Thoracic Oncology
https://www.readbyqxmd.com/read/28986666/primary-central-nervous-system-malignant-melanoma-with-leptomeningeal-melanomatosis-a-case-report-and-review-of-the-literature
#10
Kentaro Fujimori, Keiichi Sakai, Fumiko Higashiyama, Fusakazu Oya, Toshitaka Maejima, Tomomi Miyake
Leptomeningeal melanomatosis is an extremely rare variant of primary central nervous system (CNS) melanoma and has a poor prognosis and no standard treatment. Primary CNS melanoma is derived from the melanocytes of the leptomeninges. Here, we describe a case of a 37-year-old male who visited our hospital due to worsening headaches. Characteristic imaging findings of this tumor type include hyper-dense lesions that are enhanced by contrast medium on computed tomography and hyper-intensity on T1-weighted magnetic resonance images and iso- to hypo-intensity on T2-weighted magnetic resonance images...
October 6, 2017: Neurosurgical Review
https://www.readbyqxmd.com/read/28986151/braf-v600e-mutation-is-a-significant-prognosticator-of-the-tumour-regrowth-rate-in-brainstem-gangliogliomas
#11
Xin Chen, Changcun Pan, Peng Zhang, Cheng Xu, Yu Sun, Hai Yu, Yuliang Wu, Yibo Geng, Pengcheng Zuo, Zhen Wu, Junting Zhang, Liwei Zhang
BRAF V600E mutations are progression factors in paediatric low-grade gliomas. Furthermore, a high percentage of paediatric brainstem gangliogliomas have BRAF V600E mutations. However, their clinical significance, including possible connections between the biomarkers and ganglioglioma's clinical features, especially a brainstem counterpart, is unclear. To identify potential molecular features predictive of brainstem ganglioglioma's clinical outcomes, a retrospective cohort of 28 World Health Organization (WHO) grade I brainstem gangliogliomas was analysed for BRAF V600E, IDH1 R132H, and IDH2 R172K mutations, TERT C228T/C250T promoter mutation, H3F3A K27M mutation and MGMT methylation...
October 3, 2017: Journal of Clinical Neuroscience: Official Journal of the Neurosurgical Society of Australasia
https://www.readbyqxmd.com/read/28984520/prediction-of-braf-mutation-status-of-craniopharyngioma-using-magnetic-resonance-imaging-features
#12
Qi Yue, Yang Yu, Zhifeng Shi, Yongfei Wang, Wei Zhu, Zunguo Du, Zhenwei Yao, Liang Chen, Ying Mao
OBJECTIVE Treatment with a BRAF mutation inhibitor might shrink otherwise refractory craniopharyngiomas and is a promising preoperative treatment to facilitate tumor resection. The aim of this study was to investigate the noninvasive diagnosis of BRAF-mutated craniopharyngiomas based on MRI characteristics. METHODS Fifty-two patients with pathologically diagnosed craniopharyngioma were included in this study. Polymerase chain reaction was performed on tumor tissue specimens to detect BRAF and CTNNB1 mutations...
October 6, 2017: Journal of Neurosurgery
https://www.readbyqxmd.com/read/28983557/role-of-deficient-dna-mismatch-repair-status-in-patients-with-stage-iii-colon-cancer-treated-with-folfox-adjuvant-chemotherapy-a-pooled-analysis-from-2-randomized-clinical-trials
#13
Aziz Zaanan, Qian Shi, Julien Taieb, Steven R Alberts, Jeffrey P Meyers, Thomas C Smyrk, Catherine Julie, Ayman Zawadi, Josep Tabernero, Enrico Mini, Richard M Goldberg, Gunnar Folprecht, Jean Luc Van Laethem, Karine Le Malicot, Daniel J Sargent, Pierre Laurent-Puig, Frank A Sinicrope
Importance: The prognostic impact of DNA mismatch repair (MMR) status in stage III colon cancer patients receiving FOLFOX (folinic acid, fluorouracil, and oxaliplatin) adjuvant chemotherapy remains controversial. Objective: To determine the association of MMR status with disease-free survival (DFS) in patients with stage III colon cancer treated with FOLFOX. Design, Setting, and Participants: The evaluated biomarkers for MMR status were determined from prospectively collected tumor blocks from patients treated with FOLFOX in 2 open-label, phase 3 randomized clinical trials: NCCTG N0147 and PETACC8...
October 5, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28979142/the-non-small-cell-lung-cancer-egfr-extracellular-domain-mutation-m277e-is-oncogenic-and-drug-sensitive
#14
Su Yu, Yang Zhang, Yunjian Pan, Chao Cheng, Yihua Sun, Haiquan Chen
PURPOSE: To identify novel oncogenic mutations in non-small cell lung cancer patient specimens that lack mutations in known targetable genes ("pan-negative" patients). METHODS: Comprehensive mutational analyses were performed on 1,356 lung adenocarcinoma specimens. In this cohort of patients, common lung cancer oncogenic driver mutations were detected in the epidermal growth factor receptor (EGFR) kinase domain, the human epidermal growth factor receptor 2 kinase domain, as well as the KRAS, BRAF, ALK, ROS1 and RET genes...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28978720/gamma-secretase-inhibition-by-bms-906024-enhances-efficacy-of-paclitaxel-in-lung-adenocarcinoma
#15
Katherine M Morgan, Bruce S Fischer, Francis Y Lee, Jamie J Shah, Joseph R Bertino, Jeffrey Rosenfeld, Amartya Singh, Hossein Khiabanian, Sharon R Pine
Notch signaling is aberrantly activated in approximately one third of non-small cell lung cancers (NSCLC). We characterized the interaction between BMS-906024, a clinically relevant Notch gamma secretase inhibitor (GSI), and front-line chemotherapy in preclinical models of NSCLC. Chemosensitivity assays were performed on 14 human NSCLC cell lines. There was significantly greater synergy between BMS-906024 and paclitaxel than BMS-906024 and cisplatin (mean CI value = 0.54 and 0.85, respectively, P = 0.01). On an extended panel of 31 NSCLC cell lines, 25 of which were adenocarcinoma, the synergy between BMS-906024 and paclitaxel was significantly greater in KRAS- and BRAF-wildtype than KRAS- or BRAF-mutant cells (mean CI = 0...
October 4, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28976960/cancer-drug-addiction-is-relayed-by-an-erk2-dependent-phenotype-switch
#16
Xiangjun Kong, Thomas Kuilman, Aida Shahrabi, Julia Boshuizen, Kristel Kemper, Ji-Ying Song, Hans W M Niessen, Elisa A Rozeman, Marnix H Geukes Foppen, Christian U Blank, Daniel S Peeper
Observations from cultured cells, animal models and patients raise the possibility that the dependency of tumours on the therapeutic drugs to which they have acquired resistance represents a vulnerability with potential applications in cancer treatment. However, for this drug addiction trait to become of clinical interest, we must first define the mechanism that underlies it. We performed an unbiased CRISPR-Cas9 knockout screen on melanoma cells that were both resistant and addicted to inhibition of the serine/threonine-protein kinase BRAF, in order to functionally mine their genome for 'addiction genes'...
October 12, 2017: Nature
https://www.readbyqxmd.com/read/28974238/cmyc-expression-in-thyroid-follicular-cell-derived-carcinomas-a-role-in-thyroid-tumorigenesis
#17
Hany I Sakr, Deborah J Chute, Christian Nasr, Charles D Sturgis
BACKGROUND: cMYC regulates approximately 15% of human genes and is involved in up to 20% of all human cancers. Reports discussing cMYC protein expression in thyroid carcinomas are limited, with controversies pertaining to cMYC expression patterns noted in the literature. The aims of the current study were to clarify patterns and intensities of cMYC expression in follicular cell-derived thyroid carcinomas across a spectrum of cancer morphologies and disease aggressivities, to correlate cMYC with BRAF(V600E) expression, and to evaluate the potential role of cMYC in progression of well-differentiated thyroid carcinomas into less well-differentiated carcinomas...
October 3, 2017: Diagnostic Pathology
https://www.readbyqxmd.com/read/28972077/multiregional-sequencing-reveals-genomic-alterations-and-clonal-dynamics-in-primary-malignant-melanoma-of-the-esophagus
#18
Jingjing Li, Shi Yan, Zhen Liu, Yong Zhou, Yaqi Pan, Wenqing Yuan, Mengfei Liu, Qin Tan, Geng Tian, Bin Dong, Hong Cai, Nan Wu, Yang Ke
Primary malignant melanoma of the esophagus (PMME) is a rare and aggressive disease with high tendency of metastasis. To characterize the genetic basis and intra-tumor heterogeneity of PMME, we performed multiregion exome sequencing and whole genome SNP array genotyping of 12 samples obtained from a PMME patient. High intra-tumor heterogeneity was observed in both somatic mutation and copy number alteration levels. Nine geographically separate samples including two normal samples were clonally related and followed a branched evolution model...
September 29, 2017: Cancer Research
https://www.readbyqxmd.com/read/28961465/final-analysis-of-a-randomised-trial-comparing-pembrolizumab-versus-investigator-choice-chemotherapy-for-ipilimumab-refractory-advanced-melanoma
#19
Omid Hamid, Igor Puzanov, Reinhard Dummer, Jacob Schachter, Adil Daud, Dirk Schadendorf, Christian Blank, Lee D Cranmer, Caroline Robert, Anna C Pavlick, Rene Gonzalez, F Stephen Hodi, Paolo A Ascierto, April K S Salama, Kim A Margolin, Tara C Gangadhar, Ziwen Wei, Scot Ebbinghaus, Nageatte Ibrahim, Antoni Ribas
AIM: To evaluate the protocol-specified final analysis of overall survival (OS) in the KEYNOTE-002 study (NCT01704287) of pembrolizumab versus chemotherapy in patients with ipilimumab-refractory, advanced melanoma. METHODS: In this randomised, phase II study, eligible patients had advanced melanoma with documented progression after two or more ipilimumab doses, previous BRAF or MEK inhibitor or both, if BRAF(V600) mutant-positive. Patients were randomised to pembrolizumab 2 mg/kg or 10 mg/kg every 3 weeks or investigator-choice chemotherapy...
September 26, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28960623/multimodal-molecular-analysis-of-astroblastoma-enables-reclassification-of-most-cases-into-more-specific-molecular-entities
#20
Matthew D Wood, Tarik Tihan, Arie J Perry, Geeta Chacko, Clinton Turner, Cunfeng Pu, Christopher Payne, Alexander Yu, Serguei Bannykh, David A Solomon
Astroblastoma is a rare and controversial glioma with variable clinical behavior. The diagnosis currently rests on histologic findings of a circumscribed glioma with astroblastomatous pseudorosettes and vascular hyalinization. Immunohistochemical studies have suggested different oncogenic drivers, such as BRAF p.V600E, but very few cases have been studied using genome-wide methodologies. Recent genomic profiling identified a subset of CNS embryonal tumors with astroblastoma-like morphology that harbored MN1 gene fusions, termed "CNS high-grade neuroepithelial tumors with MN1 alteration" (CNS-HGNET-MN1)...
September 28, 2017: Brain Pathology
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