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https://www.readbyqxmd.com/read/28924153/common-variants-in-mmp20-at-11q22-2-predispose-to-11q-deletion-and-neuroblastoma-risk
#1
Xiao Chang, Yan Zhao, Cuiping Hou, Joseph Glessner, Lee McDaniel, Maura A Diamond, Kelly Thomas, Jin Li, Zhi Wei, Yichuan Liu, Yiran Guo, Frank D Mentch, Haijun Qiu, Cecilia Kim, Perry Evans, Zalman Vaksman, Sharon J Diskin, Edward F Attiyeh, Patrick Sleiman, John M Maris, Hakon Hakonarson
MYCN amplification and 11q deletion are two inversely correlated prognostic factors of poor outcome in neuroblastoma. Here we identify common variants at 11q22.2 within MMP20 that associate with neuroblastoma cases harboring 11q deletion (rs10895322), using GWAS in 113 European-American cases and 5109 ancestry-matched controls. The association is replicated in 44 independent cases and 1902 controls. Our study yields novel insights into the genetic underpinnings of neuroblastoma, demonstrating that the inherited common variants reported contribute to the origin of intra-tumor genetic heterogeneity in neuroblastoma...
September 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28898695/identification-of-gpc2-as-an-oncoprotein-and-candidate-immunotherapeutic-target-in-high-risk-neuroblastoma
#2
Kristopher R Bosse, Pichai Raman, Zhongyu Zhu, Maria Lane, Daniel Martinez, Sabine Heitzeneder, Komal S Rathi, Nathan M Kendsersky, Michael Randall, Laura Donovan, Sorana Morrissy, Robyn T Sussman, Doncho V Zhelev, Yang Feng, Yanping Wang, Jennifer Hwang, Gonzalo Lopez, Jo Lynne Harenza, Jun S Wei, Bruce Pawel, Tricia Bhatti, Mariarita Santi, Arupa Ganguly, Javed Khan, Marco A Marra, Michael D Taylor, Dimiter S Dimitrov, Crystal L Mackall, John M Maris
We developed an RNA-sequencing-based pipeline to discover differentially expressed cell-surface molecules in neuroblastoma that meet criteria for optimal immunotherapeutic target safety and efficacy. Here, we show that GPC2 is a strong candidate immunotherapeutic target in this childhood cancer. We demonstrate high GPC2 expression in neuroblastoma due to MYCN transcriptional activation and/or somatic gain of the GPC2 locus. We confirm GPC2 to be highly expressed on most neuroblastomas, but not detectable at appreciable levels in normal childhood tissues...
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28898690/when-lmo1-meets-mycn-neuroblastoma-is-metastatic
#3
Zhihui Liu, Carol J Thiele
LMO1 is a high-risk neuroblastoma susceptibility gene, but how LMO1 cooperates with MYCN in neuroblastoma tumorigenesis is unclear. In this issue of Cancer Cell, Zhu et al. develop a novel zebrafish model that elucidates a mechanism by which LMO1 and MYCN synergistically initiate neuroblastoma and contribute to metastatic disease progression.
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28887399/validation-of-post-induction-curie-scores-in-high-risk-neuroblastoma-a-children-s-oncology-group-cog-and-siopen-group-report-on-siopen-hr-nbl1
#4
Gregory A Yanik, Marguerite T Parisi, Arlene Naranjo, Helen Nadel, Michael J Gelfand, Julie R Park, Ruth L Ladenstein, Ulrike Poetschger, Ariane Boubaker, Dominique Valteau-Couanet, Bieke Lambert, Maria-Rita Castellani, Zvi Bar-Sever, Aurore Oudoux, Anna Kaminska, Susan G Kreissman, Barry L Shulkin, Katherine K Matthay
A semi-quantitative metaiodobenzylguanidine (mIBG) scoring method (Curie scoring, CS) was previously examined in the Children's Oncology Group (COG) high risk neuroblastoma trial, COG A3973 (A Randomized Study of Purged vs. Unpurged Peripheral Blood Stem Cell Transplant Following Dose Intensive Induction Therapy for High Risk Neuroblastoma), with a post-induction CS>2 associated with poor event free survival (EFS). The validation of Curie scoring in an independent data set, High Risk Neuroblastoma1/International Society of Pediatric Oncology European Network (SIOPEN/HR-NBL1), is now reported...
September 8, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28887356/lmo1-cooperates-with-mycn-to-promote-neuroblastomagenesis-and-metastasis
#5
(no author information available yet)
Transgenic expression of LMO1 promotes neuroblastoma metastasis in a MYCN-driven zebrafish model.
September 8, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28885700/historical-time-to-disease-progression-and-progression-free-survival-in-patients-with-recurrent-refractory-neuroblastoma-treated-in-the-modern-era-on-children-s-oncology-group-early-phase-trials
#6
Wendy B London, Rochelle Bagatell, Brenda J Weigel, Elizabeth Fox, Dongjing Guo, Collin Van Ryn, Arlene Naranjo, Julie R Park
BACKGROUND: Early-phase trials in patients with recurrent neuroblastoma historically used an objective "response" of measureable disease (Response Evaluation Criteria In Solid Tumors [RECIST], without bone/bone marrow assessment) to select agents for further study. Historical cohorts may be small and potentially biased; to the authors' knowledge, disease recurrence studies from international registries are outdated. Using a large recent cohort of patients with recurrent/refractory neuroblastoma from Children's Oncology Group (COG) modern-era early-phase trials, the authors determined outcome and quantified parameters for designing future studies...
September 8, 2017: Cancer
https://www.readbyqxmd.com/read/28881723/association-of-high-microvessel-%C3%AE-v%C3%AE-3-and-low-pten-with-poor-outcome-in-stage-3-neuroblastoma-rationale-for-using-first-in-class-dual-pi3k-brd4-inhibitor-sf1126
#7
Anat Erdreich-Epstein, Alok R Singh, Shweta Joshi, Francisco M Vega, Pinzheng Guo, Jingying Xu, Susan Groshen, Wei Ye, Melissa Millard, Mihaela Campan, Guillermo Morales, Joseph R Garlich, Peter W Laird, Robert C Seeger, Hiroyuki Shimada, Donald L Durden
Neuroblastoma (NB) is the most common extracranial solid tumor in children. Our previous studies showed that the angiogenic integrin αvβ3 was increased in high-risk metastatic (stage 4) NB compared with localized neuroblastomas. Herein, we show that integrin αvβ3 was expressed on 68% of microvessels in MYCN-amplified stage 3 neuroblastomas, but only on 34% (means) in MYCN-non-amplified tumors (p < 0.001; n = 54). PTEN, a tumor suppressor involved in αvβ3 signaling, was expressed in neuroblastomas either diffusely, focally or not at all (immunohistochemistry)...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28871274/paired-expression-analysis-of-tumor-cell-surface-antigens
#8
Rimas J Orentas, Sivasish Sindiri, Christine Duris, Xinyu Wen, Jianbin He, Jun S Wei, Jason Jarzembowski, Javed Khan
Adoptive immunotherapy with antibody-based therapy or with T cells transduced to express chimeric antigen receptors (CARs) is useful to the extent that the cell surface membrane protein being targeted is not expressed on normal tissues. The most successful CAR-based (anti-CD19) or antibody-based therapy (anti-CD20) in hematologic malignancies has the side effect of eliminating the normal B cell compartment. Targeting solid tumors may not provide a similar expendable marker. Beyond antibody to Her2/NEU and EGFR, very few antibody-based and no CAR-based therapies have seen broad clinical application for solid tumors...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28867147/lmo1-synergizes-with-mycn-to-promote-neuroblastoma-initiation-and-metastasis
#9
Shizhen Zhu, Xiaoling Zhang, Nina Weichert-Leahey, Zhiwei Dong, Cheng Zhang, Gonzalo Lopez, Ting Tao, Shuning He, Andrew C Wood, Derek Oldridge, Choong Yong Ung, Janine H van Ree, Amish Khan, Brittany M Salazar, Edroaldo Lummertz da Rocha, Mark W Zimmerman, Feng Guo, Hong Cao, Xiaonan Hou, S John Weroha, Antonio R Perez-Atayde, Donna S Neuberg, Alexander Meves, Mark A McNiven, Jan M van Deursen, Hu Li, John M Maris, A Thomas Look
A genome-wide association study identified LMO1, which encodes an LIM-domain-only transcriptional cofactor, as a neuroblastoma susceptibility gene that functions as an oncogene in high-risk neuroblastoma. Here we show that dβh promoter-mediated expression of LMO1 in zebrafish synergizes with MYCN to increase the proliferation of hyperplastic sympathoadrenal precursor cells, leading to a reduced latency and increased penetrance of neuroblastomagenesis. The transgenic expression of LMO1 also promoted hematogenous dissemination and distant metastasis, which was linked to neuroblastoma cell invasion and migration, and elevated expression levels of genes affecting tumor cell-extracellular matrix interaction, including loxl3, itga2b, itga3, and itga5...
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28860499/neuroblastoma-patient-derived-xenograft-cells-cultured-in-stem-cell-promoting-medium-retain-tumorigenic-and-metastatic-capacities-but-differentiate-in-serum
#10
Camilla U Persson, Kristoffer von Stedingk, Daniel Bexell, My Merselius, Noémie Braekeveldt, David Gisselsson, Marie Arsenian-Henriksson, Sven Påhlman, Caroline Wigerup
Cultured cancer cells serve as important models for preclinical testing of anti-cancer compounds. However, the optimal conditions for retaining original tumor features during in vitro culturing of cancer cells have not been investigated in detail. Here we show that serum-free conditions are critical for maintaining an immature phenotype of neuroblastoma cells isolated from orthotopic patient-derived xenografts (PDXs). PDX cells could be grown either as spheres or adherent on laminin in serum-free conditions with retained patient-specific genomic aberrations as well as tumorigenic and metastatic capabilities...
August 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28845131/results-of-neuroblastoma-treatment-in-lithuania-a-single-centre-experience
#11
Austėja Juškaitė, Indrė Tamulienė, Jelena Rascon
BACKGROUND: Neuroblastoma (NB) is the most common extracranial solid tumour in children. This is a very rare disease with heterogeneous biology varying from complete spontaneous regression to a highly aggressive tumour responsible for 15% of malignancy-related death in early childhood. Analyses of survival rates in Europe have shown a considerable difference between Northern/Western and Eastern European countries. Treatment results of NB in Lithuania have never been analyzed. AIM: To assess the survival rate of children with NB according to initial spread of the disease, age at diagnosis, the MYCN amplification, risk group, and treatment period...
2017: Acta medica Lituanica
https://www.readbyqxmd.com/read/28825729/a-children-s-oncology-group-and-target-initiative-exploring-the-genetic-landscape-of-wilms-tumor
#12
Samantha Gadd, Vicki Huff, Amy L Walz, Ariadne H A G Ooms, Amy E Armstrong, Daniela S Gerhard, Malcolm A Smith, Jaime M Guidry Auvil, Daoud Meerzaman, Qing-Rong Chen, Chih Hao Hsu, Chunhua Yan, Cu Nguyen, Ying Hu, Leandro C Hermida, Tanja Davidsen, Patee Gesuwan, Yussanne Ma, Zusheng Zong, Andrew J Mungall, Richard A Moore, Marco A Marra, Jeffrey S Dome, Charles G Mullighan, Jing Ma, David A Wheeler, Oliver A Hampton, Nicole Ross, Julie M Gastier-Foster, Stefan T Arold, Elizabeth J Perlman
We performed genome-wide sequencing and analyzed mRNA and miRNA expression, DNA copy number, and DNA methylation in 117 Wilms tumors, followed by targeted sequencing of 651 Wilms tumors. In addition to genes previously implicated in Wilms tumors (WT1, CTNNB1, AMER1, DROSHA, DGCR8, XPO5, DICER1, SIX1, SIX2, MLLT1, MYCN, and TP53), we identified mutations in genes not previously recognized as recurrently involved in Wilms tumors, the most frequent being BCOR, BCORL1, NONO, MAX, COL6A3, ASXL1, MAP3K4, and ARID1A...
August 21, 2017: Nature Genetics
https://www.readbyqxmd.com/read/28818093/case-report-value-of-gene-expression-profiling-in-the-diagnosis-of-atypical-neuroblastoma
#13
Anne C Harttrampf, Qingrong Chen, Eva Jüttner, Julia Geiger, Gordon Vansant, Javed Khan, Udo Kontny
BACKGROUND: Nephroblastoma and neuroblastoma belong to the most common abdominal malignancies in childhood. Similarities in the initial presentation may provide difficulties in distinguishing between these two entities, especially if unusual variations to prevalent patterns of disease manifestation occur. Because of the risk of tumor rupture, European protocols do not require biopsy for diagnosis, which leads to misdiagnosis in some cases. CASE PRESENTATION: We report on a 4½-year-old girl with a renal tumor displaying radiological and laboratory characteristics supporting the diagnosis of nephroblastoma...
August 17, 2017: BMC Research Notes
https://www.readbyqxmd.com/read/28808732/individualized-risk-assessment-in-neuroblastoma-does-the-tumoral-metabolic-activity-on-123-i-mibg-spect-predict-the-outcome
#14
Julian M M Rogasch, Patrick Hundsdoerfer, Christian Furth, Florian Wedel, Frank Hofheinz, Paul-Christian Krüger, Holger Lode, Winfried Brenner, Angelika Eggert, Holger Amthauer, Imke Schatka
PURPOSE: Risk-adapted treatment in children with neuroblastoma (NB) is based on clinical and genetic factors. This study evaluated the metabolic tumour volume (MTV) and its asphericity (ASP) in pretherapeutic (123)I-MIBG SPECT for individualized image-based prediction of outcome. METHODS: This retrospective study included 23 children (11 girls, 12 boys; median age 1.8 years, range 0.3-6.8 years) with newly diagnosed NB consecutively examined with pretherapeutic (123)I-MIBG SPECT...
August 14, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28807939/prc2-mediated-transcriptomic-alterations-at-the-embryonic-stage-govern-tumorigenesis-and-clinical-outcome-in-mycn-driven-neuroblastoma
#15
Shoma Tsubota, Satoshi Kishida, Teppei Shimamura, Miki Ohira, Satoshi Yamashita, Dongliang Cao, Shinichi Kiyonari, Toshikazu Ushijima, Kenji Kadomatsu
Pediatric cancers such as neuroblastoma are thought to involve a dysregulation of embryonic development. However, it has been difficult to identify the critical events that trigger tumorigenesis and differentiate them from normal development. In this study, we report the establishment of a spheroid culture method that enriches early-stage tumor cells from TH-MYCN mice, a preclinical model of neuroblastoma. Using this method, we found that tumorigenic cells were evident as early as day E13.5 during embryo development, when the MYC and PRC2 transcriptomes were significantly altered...
August 14, 2017: Cancer Research
https://www.readbyqxmd.com/read/28796037/functional-prediction-of-mir-3144-5p-in-human-cardiac-myocytes-based-on-transcriptome-sequencing-and-bioinformatics
#16
Lei Ruan, Yi Yang, Yi Huang, Ling Ding, Cuntai Zhang, Xiaofen Wu
BACKGROUND: RAN guanine nucleotide release factor (RANGRF) encoding protein MOG1 plays an important role in cardiac arrhythmia, so we intended to investigate the regulatory miRNA of RANGRF and explore its potential regulatory mechanism in arrhythmogenesis. METHODS: Based on bioinformatic analysis, miR-3144-5p was predicted to be a regulatory miRNA of RANGRF, which were then validated through a dual-luciferase reporter plasmid assay. Subsequently, the expression level of miR-3144-5p in human cardiac myocytes (HCMs) was detected, followed by cell transfection with miR-3144-5p mimics...
August 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28791558/zar1-knockdown-promotes-the-differentiation-of-human-neuroblastoma-cells-by-suppression-of-mycn-expression
#17
Yosuke Watanabe, Yoshiaki Ishizuka, Takayuki Hirano, Eri Nagasaki-Maeoka, Reina Hoshi, Shinsuke Yoshizawa, Shota Uekusa, Hiroyuki Kawashima, Kiminobu Sugito, Kenichi Shinohara, Noboru Fukuda, Hiroki Nagase, Masayoshi Soma, Tsugumichi Koshinaga, Kyoko Fujiwara
Although DNA hypermethylation at non-promoter region of the Zygote arrest 1 (ZAR1) gene has been observed in many types of tumor, including neuroblastoma (NB), the role of this gene in tumor development and/or progression is unclear. One reason is that knowledge about the function of ZAR1 protein is limited. Although it has been reported that ZAR1 plays a crucial role in early embryogenesis and may act as a transcriptional repressor for some transcripts, the detailed mechanism is still elusive. In the present study, we analyzed public data of NB patients and found that higher expression levels of ZAR1 were significantly associated with a shorter survival period...
August 8, 2017: Medical Oncology
https://www.readbyqxmd.com/read/28768907/upregulated-heme-biosynthesis-an-exploitable-vulnerability-in-mycn-driven-leukemogenesis
#18
Yu Fukuda, Yao Wang, Shangli Lian, John Lynch, Shinjiro Nagai, Bruce Fanshawe, Ayten Kandilci, Laura J Janke, Geoffrey Neale, Yiping Fan, Brian P Sorrentino, Martine F Roussel, Gerard Grosveld, John D Schuetz
The increased heme biosynthesis long observed in leukemia was previously of unknown significance. Heme, synthesized from porphyrin precursors, plays a central role in oxygen metabolism and mitochondrial function, yet little is known about its role in leukemogenesis. Here, we show increased expression of heme biosynthetic genes, including UROD, only in pediatric AML samples that have high MYCN expression. High expression of both UROD and MYCN predicts poor overall survival and unfavorable outcomes in adult AML...
August 3, 2017: JCI Insight
https://www.readbyqxmd.com/read/28767324/eef2k-protects-mycn-amplified-cells-from-starvation
#19
Alberto Delaidelli, Gabriel Leprivier, Poul H Sorensen
No abstract text is available yet for this article.
September 17, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28753576/isoxazole-compound-ml327-blocks-myc-expression-and-tumor-formation-in-neuroblastoma
#20
Eric J Rellinger, Chandrasekhar Padmanabhan, Jingbo Qiao, Brian T Craig, Hanbing An, Jing Zhu, Hernán Correa, Alex G Waterson, Craig W Lindsley, R Daniel Beauchamp, Dai H Chung
Neuroblastomas are the most common extracranial solid tumors in children and arise from the embryonic neural crest. MYCN-amplification is a feature of ~30% of neuroblastoma tumors and portends a poor prognosis. Neural crest precursors undergo epithelial-to-mesenchymal transition (EMT) to gain migratory potential and populate the sympathoadrenal axis. Neuroblastomas are posited to arise due to a blockade of neural crest differentiation. We have recently reported effects of a novel MET inducing compound ML327 (N-(3-(2-hydroxynicotinamido) propyl)-5-phenylisoxazole-3-carboxamide) in colon cancer cells...
July 20, 2017: Oncotarget
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