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https://www.readbyqxmd.com/read/29141318/-ras-associated-autoimmune-leukoproliferative-disorder-a-report-of-2-cases-and-literature-review
#1
T Y He, C R Li, Y Xia, F F Liang, Y Luo, J Yang
Objective: To investigate the clinical features and genetic characteristics of cases with Ras-associated autoimmune leukoproliferative disorder(RALD). Method: Characteristics of clinical data and gene mutation of the first two cases in China with RALD were retrospectively analyzed. The related literature was searched by using search terms "NRAS" , "KRAS" or "RALD" . Result: Case1, a seven-year-seven-month old girl, was admitted due to "thrombocytopenia and splenomegaly for three years" . Palpation showed enlargement of submandibular lymph nodes and hepatosplenomegaly...
November 2, 2017: Zhonghua Er Ke za Zhi. Chinese Journal of Pediatrics
https://www.readbyqxmd.com/read/29141224/genetic-and-genomic-characterization-of-462-melanoma-patient-derived-xenografts-tumor-biopsies-and-cell-lines
#2
Bradley Garman, Ioannis N Anastopoulos, Clemens Krepler, Patricia Brafford, Katrin Sproesser, Yuchao Jiang, Bradley Wubbenhorst, Ravi Amaravadi, Joseph Bennett, Marilda Beqiri, David Elder, Keith T Flaherty, Dennie T Frederick, Tara C Gangadhar, Michael Guarino, David Hoon, Giorgos Karakousis, Qin Liu, Nandita Mitra, Nicholas J Petrelli, Lynn Schuchter, Batool Shannan, Carol L Shields, Jennifer Wargo, Brandon Wenz, Melissa A Wilson, Min Xiao, Wei Xu, Xaiowei Xu, Xiangfan Yin, Nancy R Zhang, Michael A Davies, Meenhard Herlyn, Katherine L Nathanson
Tumor-sequencing studies have revealed the widespread genetic diversity of melanoma. Sequencing of 108 genes previously implicated in melanomagenesis was performed on 462 patient-derived xenografts (PDXs), cell lines, and tumors to identify mutational and copy number aberrations. Samples came from 371 unique individuals: 263 were naive to treatment, and 108 were previously treated with targeted therapy (34), immunotherapy (54), or both (20). Models of all previously reported major melanoma subtypes (BRAF, NRAS, NF1, KIT, and WT/WT/WT) were identified...
November 14, 2017: Cell Reports
https://www.readbyqxmd.com/read/29138054/keratinocyte-sonic-hedgehog-up-regulation-drives-the-development-of-giant-congenital-nevi-via-paracrine-endothelin-1-secretion
#3
Arash Chitsazan, Blake Ferguson, Rehan Villani, Herlina Y Handoko, Pamela Mukhopadhyay, Brian Gabrielli, Wolter J Mooi, H Peter Soyer, Duncan Lambie, Kiarash Khosrotehrani, Grant Morahan, Graeme J Walker
Giant congenital nevi are associated with clinical complications such as neurocutaneous melanosis and melanoma. Virtually nothing is known about why some individuals develop these lesions. We previously identified the sonic hedgehog (Shh) pathway regulator Cdon as a candidate nevus modifier gene. Here we validate this by studying Cdon knockout mice, and go on to establishment the mechanism by which Shh exacerbates nevogenesis. Cdon knockout mice develop blue nevi without the need for somatic melanocyte oncogenic mutation...
November 11, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29137279/implications-of-mutational-spectrum-in-myelodysplastic-syndromes-based-on-targeted-next-generation-sequencing
#4
Yuanyuan Xu, Yan Li, Qingyu Xu, Yuelong Chen, Na Lv, Yu Jing, Liping Dou, Jian Bo, Guangyuan Hou, Jing Guo, Xiuli Wang, Lili Wang, Yonghui Li, Chongjian Chen, Li Yu
Myelodysplastic syndromes (MDS) are a group of myeloid hematological malignancies, with a high risk of progression to acute myeloid leukemia (AML). To explore the role of acquired mutations in MDS, 111 MDS-associated genes were screened using next-generation sequencing (NGS), in 125 patients. One or more mutations were detected in 84% of the patients. Some gene mutations are specific for MDS and were associated with disease subtypes, and the patterns of mutational pathways could be associated with progressive MDS...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29136733/-exploratory-study-of-circulating-tumor-dna-detection-in-early-breast-cancer-an-analysis-of-75-next-generation-sequencing-results
#5
B Zhou, L Xin, L Xu, Y H Liu, M M Zhang, R L Jing, X Y Liang, S B Cao
Objective: To explore the utility of circulating tumor DNA detection in early breast cancer by using next-generation sequencing. Methods: This exploratory study of circulating tumor DNA detection is for early invasive breast cancer patients treated in Breast Disease Center, Peking University First Hospital from December 2015 to July 2016. Plasma samples were collected and were used to isolate plasma cell-free DNA.Exons or hotspots of 247 cancer related genes were sequenced by next-generation sequencing. Mutations and their correlation with clinic-pathological factors were analyzed...
November 1, 2017: Zhonghua Wai Ke za Zhi [Chinese Journal of Surgery]
https://www.readbyqxmd.com/read/29133622/ceritinib-enhances-the-efficacy-of-trametinib-in-braf-nras-wild-type-melanoma-cell-lines
#6
Daniel Verduzco, Brent M Kuenzi, Fumi Kinose, Vernon K Sondak, Zeynep Eroglu, Uwe Rix, Keiran S M Smalley
Targeted therapy options are currently lacking for the heterogeneous population of patients whose melanomas lack BRAF or NRAS mutations (~35% of cases). We undertook a chemical biology screen to identify potential novel drug targets for this understudied group of tumors. Screening a panel of 8 BRAF/NRAS-WT melanoma cell lines against 240 targeted drugs identified ceritinib and trametinib as potential hits with single agent activity. Ceritinib enhanced the efficacy of trametinib across the majority of the BRAF/NRAS-WT cell lines, and the combination showed increased cytotoxicity in both 3D spheroid culture and long-term colony formation experiments...
November 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/29129743/comprehensive-identification-of-proteins-binding-to-rna-g-quadruplex-motifs-in-the-5-utr-of-tumor-associated-mrnas
#7
Tatsuo Serikawa, Christos Spanos, Annekathrin von Hacht, Nediljko Budisa, Juri Rappsilber, Jens Kurreck
G-quadruplex structures in the 5' UTR of mRNAs are widely considered to suppress translation without affecting transcription. The current study describes the comprehensive analysis of proteins binding to four different G-quadruplex motifs located in mRNAs of the cancer-related genes Bcl-2, NRAS, MMP16, and ARPC2. Following metabolic labeling (Stable Isotope Labeling with Amino acids in Cell culture, SILAC) of proteins in the human cell line HEK293, G-quadruplex binding proteins were enriched by pull-down assays and identified by LC-orbitrap mass spectrometry...
November 9, 2017: Biochimie
https://www.readbyqxmd.com/read/29128266/molecular-profiling-of-patients-with-advanced-colorectal-cancer-princess-margaret-cancer-centre-experience
#8
Joanne W Chiu, Monika K Krzyzanowska, Stefano Serra, Jennifer J Knox, Neesha C Dhani, Helen Mackay, David Hedley, Malcolm Moore, Geoffrey Liu, Ronald L Burkes, Christine Brezden-Masley, Michael H Roehrl, Kenneth J Craddock, Ming-Sound Tsao, Tong Zhang, Celeste Yu, Suzanne Kamel-Reid, Lillian L Siu, Philippe L Bedard, Eric X Chen
BACKGROUND: Molecular aberrations in KRAS, NRAS, BRAF, and PIK3CA have been well-described in advanced colorectal cancer. The incidences of other mutations are less known. We report results of molecular profiling of advanced colorectal cancer in an academic cancer center. PATIENTS AND METHODS: Patients with advanced colorectal were enrolled in an institution-wide molecular profiling program. Profiling was performed on formalin-fixed paraffin embedded archival tissues using a customized MassArray panel (23 genes, 279 mutations) or the Illumina MiSeq TruSeq Cancer Panel (48 genes, 212 amplicons, ≥ 500× coverage) in a Clinical Laboratory Improvement Amendments-certified laboratory...
October 23, 2017: Clinical Colorectal Cancer
https://www.readbyqxmd.com/read/29126472/a-novel-visible-light-driven-photoelectrochemical-immunosensor-based-on-multi-amplification-strategy-for-ultrasensitive-detection-of-microcystin-lr
#9
Jie Wei, Aori Qileng, Yun Yan, Hongtao Lei, Shengsen Zhang, Weipeng Liu, Yingju Liu
An ultrasensitive photoelectrochemical (PEC) immunoassay based on multiple signal amplification strategy was fabricated for the detection of microcystin-LR (MC-LR). The CdS/TiO2 nanorod arrays (CdS/TiO2 NRAs) modified FTO electrode, which can weaken the self-oxidation by photogenerated holes of CdS nanoparticles, and limit the recombination of electron-hole pairs and broaden optical absorption of TiO2 NRAs, was used as a visible-light driven material to immobilize antigens. Then, Fe3O4 nanoparticles/polydopamine (Fe3O4@PDA) was used as the carrier to load secondary antibody (Ab2) and horseradish peroxidase (HRP), where Fe3O4 nanoparticles and HRP can synergistically accelerate the oxidation of 4-chloro-1-naphthol (4-CN) by H2O2 to produce biocatalytic precipitation (BCP) on the surface of modified electrode...
November 22, 2017: Analytica Chimica Acta
https://www.readbyqxmd.com/read/29121869/ablation-of-epidermal-rxr%C3%AE-in-cooperation-with-activated-cdk4-and-oncogenic-nras-generates-spontaneous-and-acute-neonatal-uvb-induced-malignant-metastatic-melanomas
#10
Sharmeen Chagani, Rong Wang, Evan L Carpenter, Christiane V Löhr, Gitali Ganguli-Indra, Arup K Indra
BACKGROUND: Understanding the underlying molecular mechanisms involved in the formation of cutaneous malignant melanoma is critical for improved diagnosis and treatment. Keratinocytic nuclear receptor Retinoid X Receptor α (RXRα) has a protective role against melanomagenesis and is involved in the regulation of keratinocyte and melanocyte homeostasis subsequent acute ultraviolet (UV) irradiation. METHODS: We generated a trigenic mouse model system (RXRα (ep-/-) | Tyr-NRAS (Q61K) | CDK4 (R24C/R24C) ) harboring an epidermal knockout of Retinoid X Receptor α (RXRα (ep-/-) ), combined with oncogenic NRAS (Q61K) (constitutively active RAS) and activated CDK4 (R24C/R24C) (constitutively active CDK4)...
November 9, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29121185/molecular-characteristics-of-conjunctival-melanoma-using-whole-exome-sequencing
#11
Swarup S Swaminathan, Matthew G Field, David Sant, Gaofeng Wang, Anat Galor, Sander R Dubovy, J William Harbour, Carol L Karp
Importance: Conjunctival melanoma (CM) is a highly aggressive ocular cancer for which treatment options are limited; the molecular pathogenesis is poorly understood. Objective: To identify the molecular characteristics of CM using next-generation whole-exome sequencing (WES). Design, Setting, and Participants: Whole-exome sequencing was performed on tumor DNA extracted from the archived specimens of 5 patients with CM who had been treated with surgical excision between 2006 and 2011...
November 9, 2017: JAMA Ophthalmology
https://www.readbyqxmd.com/read/29117310/sequencing-and-phasing-cancer-mutations-in-lung-cancers-using-a-long-read-portable-sequencer
#12
Ayako Suzuki, Mizuto Suzuki, Junko Mizushima-Sugano, Martin C Frith, Wojciech Makalowski, Takashi Kohno, Sumio Sugano, Katsuya Tsuchihara, Yutaka Suzuki
Here, we employed cDNA amplicon sequencing using a long-read portable sequencer, MinION, to characterize various types of mutations in cancer-related genes, namely, EGFR, KRAS, NRAS and NF1. For homozygous SNVs, the precision and recall rates were 87.5% and 91.3%, respectively. For previously reported hotspot mutations, the precision and recall rates reached 100%. The precise junctions of EML4-ALK, CCDC6-RET and five other gene fusions were also detected. Taking advantages of long-read sequencing, we conducted phasing of EGFR mutations and elucidated the mutational allelic backgrounds of anti-tumor drug-sensitive and resistant mutations, which could provide useful information for selecting therapeutic approaches...
June 27, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/29115360/environmentally-benign-synthesis-of-cuins2-zno-heteronanorods-visible-light-activated-photocatalysis-of-organic-pollutant-bacteria-and-study-of-its-mechanism
#13
Minki Baek, Eun-Ju Kim, Seok Won Hong, Wooyul Kim, Kijung Yong
Due to its high light absorption coefficient and appropriate bandgap, CuInS2 (CIS) has been receiving much attention as an absorber material for thin film solar cells and also as a visible light photocatalyst. Herein we present heterostructured CIS/ZnO nanorods (NRs) in an attempt to enhance light absorption and facilitate charge separation/transfer in the photocatalysis system. CIS nanoparticles (NPs) were directly deposited on ZnO nanorod arrays (NRAs) to fabricate heterostructured CIS/ZnO NRAs using an environmentally benign, non-hydrazine solution reaction...
November 8, 2017: Photochemical & Photobiological Sciences
https://www.readbyqxmd.com/read/29113722/the-landscape-of-somatic-mutations-in-indonesian-cervical-cancer-is-predominated-by-the-pi3k-pathway
#14
Vivian M Spaans, I Nyoman Bayu Mahendra, Gatot Purwoto, Marjolijn D Trietsch, Michelle Osse, Natalja Ter Haar, Alexander A W Peters, Gert J Fleuren, Ekaterina S Jordanova
OBJECTIVE: To investigate the prevalence of somatic mutations in Indonesian cervical carcinoma patients in the context of histology and human papillomavirus (HPV) type. METHODS: In total 174 somatic hot-spot mutations in 13 genes were analyzed by mass spectrometry in 137 Indonesian cervical carcinomas. RESULTS: In 66/137 tumors (48%) 95 mutations were identified. PIK3CA was most frequently mutated (24%), followed by FBXW7 (7%), CTNNB1 (6%), and PTEN (6%)...
November 4, 2017: Gynecologic Oncology
https://www.readbyqxmd.com/read/29113686/down-regulation-of-mir-26a-5p-in-hepatocellular-carcinoma-a-qrt-pcr-and-bioinformatics-study
#15
Liang Liang, Jiang-Hui Zeng, Jie-Yu Wang, Rong-Quan He, Jie Ma, Gang Chen, Xiao-Yong Cai, Xiao-Hua Hu
BACKGROUND: To practically verify the clinical value of miR-26a-5p and thoroughly explore its target genes as well as its potential functions in hepatocellular carcinoma (HCC). METHODS: HCC and adjacent non-cancerous hepatic tissues of 95 HCC patients were collected for analysis using reverse transcription quantitative real-time PCR (qRT-PCR). For the bioinformatics analysis, we identified potential target genes for miR-26a-5p from differentially expressed genes (DEGs) in Gene Expression Omnibus (GEO) data sets and miRWalk predicted database...
October 10, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29112787/dabrafenib-inhibits-the-growth-of-braf-wt-cancers-through-cdk16-and-nek9-inhibition
#16
Manali Phadke, Lily L Remsing Rix, Inna Smalley, Annamarie T Bryant, Yunting Luo, Harshani R Lawrence, Braydon J Schaible, Y Ann Chen, Uwe Rix, Keiran S M Smalley
Although the BRAF inhibitors dabrafenib and vemurafenib have both proven successful against BRAF-mutant melanoma, there seem to be differences in their mechanisms of action. Here, we show that dabrafenib is more effective at inhibiting the growth of NRAS-mutant and KRAS-mutant cancer cell lines than vemurafenib. Using mass spectrometry-based chemical proteomics we identified NEK9 and CDK16 as unique targets of dabrafenib. Both NEK9 and CDK16 were highly expressed in specimens of advanced melanoma, with high expression of both proteins correlating with a worse overall survival...
November 7, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/29112704/circulating-tumor-dna-predicts-survival-in-patients-with-resected-high-risk-stage-ii-iii-melanoma
#17
R J Lee, G Gremel, A Marshall, K A Myers, N Fisher, J Dunn, N Dhomen, P G Corrie, M R Middleton, P Lorigan, R Marais
Background: Patients with high-risk stage II/III resected melanoma commonly develop distant metastases. At present, we cannot differentiate between patients who will recur or those who are cured by surgery. We investigated if circulating tumor DNA (ctDNA) can predict relapse and survival in patients with resected melanoma. Patients and methods: We performed droplet digital polymerase chain reaction to detect BRAF and NRAS mutations in plasma taken after surgery from 161 stage II/III high-risk melanoma patients enrolled in the AVAST-M adjuvant trial...
November 3, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29103024/long-term-survivors-of-pancreatic-adenocarcinoma-show-low-rates-of-genetic-alterations-in-kras-tp53-and-smad4
#18
Michele Masetti, Giorgia Acquaviva, Michela Visani, Giovanni Tallini, Adele Fornelli, Moira Ragazzi, Francesco Vasuri, Daniela Grifoni, Simone Di Giacomo, Sirio Fiorino, Raffaele Lombardi, David Tuminati, Matteo Ravaioli, Carlo Fabbri, Maria Letizia Bacchi-Reggiani, Annalisa Pession, Elio Jovine, Dario de Biase
BACKGROUND: Pancreatic adenocarcinoma (PDAC) is one of the deadliest human malignancies. Although surgery is currently the only effective treatment for PDAC, most patients survive less than 20 months after tumor resection. OBJECTIVE: The primary goal was to investigate alterations in KRAS, TP53, SMAD4 and CDKN2A/p16 in tumors from patients with exceptionally long survival after surgery. METHODS: Tumors from 15 patients with PDAC that survived more than 55 months after surgery ("LS") were analyzed for KRAS, TP53, IDH1, NRAS and BRAF using next-generation sequencing...
October 27, 2017: Cancer Biomarkers: Section A of Disease Markers
https://www.readbyqxmd.com/read/29101736/clinical-implications-of-nras-overexpression-in-resectable-pancreatic-adenocarcinoma-patients
#19
Javier Martinez-Useros, Weiyao Li, Tihomir Georgiev-Hristov, Maria J Fernandez-Aceñero, Aurea Borrero-Palacios, Nuria Perez, Angel Celdran, Jesus Garcia-Foncillas
Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer, and its incidence is rising worldwide. Although survival can be improved by surgical resection, when detected at an early stage, this type of cancer is usually asymptomatic, and disease becomes only apparent after metastasis. Adjuvant treatment does not improve survival, thus after surgery there is a lack of predictive and prognosis biomarkers to predict treatment response and survival. The mitogen-activated protein-kinase and phosphoinositide 3-kinase signalling pathways play a crucial role in cancer development and progression...
November 3, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/29097261/calmodulin-and-iqgap1-activation-of-pi3k%C3%AE-and-akt-in-kras-hras-and-nras-driven-cancers
#20
REVIEW
Ruth Nussinov, Mingzhen Zhang, Chung-Jung Tsai, Hyunbum Jang
Calmodulin (CaM) binds only oncogenic KRas, but not HRas or NRas, and thus contributes only to KRAS-driven cancers. How CaM interacts with KRas and how it boosts KRAS cancers are among the most coveted aims in cancer biology. Here we address this question, and further ask: Are there proteins that can substitute for CaM in HRAS- and NRAS-driven cancers? Can scaffolding protein IQGAP1 be one? Data suggest that formation of a CaM-KRas-PI3Kα ternary complex promotes full PI3Kα activation, and thereby potent PI3Kα/Akt/mTOR proliferative signaling...
October 31, 2017: Biochimica et Biophysica Acta
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