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https://www.readbyqxmd.com/read/29117357/evaluation-of-genetic-predisposition-for-mycn-amplified-neuroblastoma
#1
Eric A Hungate, Mark A Applebaum, Andrew D Skol, Zalman Vaksman, Maura Diamond, Lee McDaniel, Samuel L Volchenboum, Barbara E Stranger, John M Maris, Sharon J Diskin, Kenan Onel, Susan L Cohn
To investigate genetic predispositions for MYCN-amplified neuroblastoma, we performed a meta-analysis of three genome-wide association studies totaling 615 MYCN-amplified high-risk neuroblastoma cases and 1869 MYCN-nonamplified non-high-risk neuroblastoma cases as controls using a fixed-effects model with inverse variance weighting. All statistical tests were two-sided. We identified a novel locus at 3p21.31 indexed by the single nucleotide polymorphism (SNP) rs80059929 (odds ratio [OR] = 2.95, 95% confidence interval [CI] = 2...
October 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29029458/lmo1-polymorphisms-reduce-neuroblastoma-risk-in-chinese-children-a-two-center-case-control-study
#2
Jiao Zhang, Huiran Lin, Jiaxiang Wang, Jing He, Da Zhang, Pan Qin, Lin Yang, Lizhao Yan
Previous genome-wide association and validation studies suggest that LIM domain only 1 (LMO1) gene polymorphisms affect neuroblastoma susceptibility. In this work, we used Taqman methodology to genotype four LMO1 polymorphisms (rs110419 A > G, rs4758051 G > A, rs10840002 A > G and rs204938 A > G) in 118 neuroblastoma cases and 281 controls from Northern China. Odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the association. We found that rs4758051 G > A was associated with a decreased neuroblastoma risk (AA vs...
September 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/29024823/genetic-variations-of-gwas-identified-genes-and-neuroblastoma-susceptibility-a-replication-study-in-southern-chinese-children
#3
Jing He, Yan Zou, Tongmin Wang, Ruizhong Zhang, Tianyou Yang, Jinhong Zhu, Fenghua Wang, Huimin Xia
Neuroblastoma is one of the most commonly diagnosed solid cancers for children, and genetic factors may play a critical role in neuroblastoma development. Previous genome-wide association studies (GWASs) have identified nine genes associated with neuroblastoma susceptibility in Caucasians. To determine whether genetic variations in these genes are also associated with neuroblastoma susceptibility in Southern Chinese children, we genotyped 25 polymorphisms within these genes by the TaqMan method in 256 cases and 531 controls...
December 2017: Translational Oncology
https://www.readbyqxmd.com/read/28898690/when-lmo1-meets-mycn-neuroblastoma-is-metastatic
#4
COMMENT
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/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/28881592/associations-between-lmo1-gene-polymorphisms-and-wilms-tumor-susceptibility
#6
Guo-Chang Liu, Zhen-Jian Zhuo, Shi-Bo Zhu, Jinhong Zhu, Wei Jia, Zhang Zhao, Jin-Hua Hu, Jing He, Feng-Hua Wang, Wen Fu
Wilms' tumor is the most common childhood renal malignancy. A genome-wide association study identified LIM domain only 1 (LMO1) as having oncogenic potential. We examined the associations between LMO1 gene polymorphisms and susceptibility to Wilms' tumor. In this hospital-based, case-control study, we recruited 145 children with Wilms' tumor and 531 cancer-free children. Four polymorphisms (rs110419 A>G, rs4758051 G>A, rs10840002 A>G and rs204938 A>G) were genotyped using Taqman methodology. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure the associations between selected polymorphisms and Wilms' tumor susceptibility...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28867147/lmo1-synergizes-with-mycn-to-promote-neuroblastoma-initiation-and-metastasis
#7
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/28854983/identification-of-cis-regulatory-mutations-generating-de-novo-edges-in-personalized-cancer-gene-regulatory-networks
#8
Zeynep Kalender Atak, Hana Imrichova, Dmitry Svetlichnyy, Gert Hulselmans, Valerie Christiaens, Joke Reumers, Hugo Ceulemans, Stein Aerts
The identification of functional non-coding mutations is a key challenge in the field of genomics. Here we introduce μ-cisTarget to filter, annotate and prioritize cis-regulatory mutations based on their putative effect on the underlying "personal" gene regulatory network. We validated μ-cisTarget by re-analyzing the TAL1 and LMO1 enhancer mutations in T-ALL, and the TERT promoter mutation in melanoma. Next, we re-sequenced the full genomes of ten cancer cell lines and used matched transcriptome data and motif discovery to identify master regulators with de novo binding sites that result in the up-regulation of nearby oncogenic drivers...
August 30, 2017: Genome Medicine
https://www.readbyqxmd.com/read/28768142/contributions-of-ikzf1-ddc-cdkn2a-cebpe-and-lmo1-gene-polymorphisms-to-acute-lymphoblastic-leukemia-in-a-yemeni-population
#9
Boshra Al-Absi, Muhammad F M Razif, Suzita M Noor, Riyadh Saif-Ali, Mohammed Aqlan, Sameer D Salem, Radwan H Ahmed, Sekaran Muniandy
BACKGROUND: Genome-wide and candidate gene association studies have previously revealed links between a predisposition to acute lymphoblastic leukemia (ALL) and genetic polymorphisms in the following genes: IKZF1 (7p12.2; ID: 10320), DDC (7p12.2; ID: 1644), CDKN2A (9p21.3; ID: 1029), CEBPE (14q11.2; ID: 1053), and LMO1 (11p15; ID: 4004). In this study, we aimed to conduct an investigation into the possible association between polymorphisms in these genes and ALL within a sample of Yemeni children of Arab-Asian descent...
October 2017: Genetic Testing and Molecular Biomarkers
https://www.readbyqxmd.com/read/28445865/associations-between-lmo1-gene-polymorphisms-and-wilms-tumor-susceptibility
#10
Guo-Chang Liu, Zhen-Jian Zhuo, Shi-Bo Zhu, Jinhong Zhu, Wei Jia, Zhang Zhao, Jin-Hua Hu, Jing He, Feng-Hua Wang, Wen Fu
Wilms' tumor is the most common childhood renal malignancy. A genome-wide association study identified LIM domain only 1 (LMO1) as having oncogenic potential. We examined the associations between LMO1 gene polymorphisms and susceptibility to Wilms' tumor. In this hospital-based, case-control study, we recruited 145 children with Wilms' tumor and 531 cancer-free children. Four polymorphisms (rs110419 A>G, rs4758051 G>A, rs10840002 A>G and rs204938 A>G) were genotyped using Taqman methodology. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure the associations between selected polymorphisms and Wilms' tumor susceptibility...
April 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28260788/apobec-signature-mutation-generates-an-oncogenic-enhancer-that-drives-lmo1-expression-in-t-all
#11
Z Li, B J Abraham, A Berezovskaya, N Farah, Y Liu, T Leon, A Fielding, S H Tan, T Sanda, A S Weintraub, B Li, S Shen, J Zhang, M R Mansour, R A Young, A T Look
Oncogenic driver mutations are those that provide a proliferative or survival advantage to neoplastic cells, resulting in clonal selection. Although most cancer-causing mutations have been detected in the protein-coding regions of the cancer genome; driver mutations have recently also been discovered within noncoding genomic sequences. Thus, a current challenge is to gain precise understanding of how these unique genomic elements function in cancer pathogenesis, while clarifying mechanisms of gene regulation and identifying new targets for therapeutic intervention...
October 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27797342/high-throughput-screening-in-niche-based-assay-identifies-compounds-to-target-preleukemic-stem-cells
#12
Bastien Gerby, Diogo F T Veiga, Jana Krosl, Sami Nourreddine, Julianne Ouellette, André Haman, Geneviève Lavoie, Iman Fares, Mathieu Tremblay, Véronique Litalien, Elizabeth Ottoni, Milena Kosic, Dominique Geoffrion, Joël Ryan, Paul S Maddox, Jalila Chagraoui, Anne Marinier, Josée Hébert, Guy Sauvageau, Benjamin H Kwok, Philippe P Roux, Trang Hoang
Current chemotherapies for T cell acute lymphoblastic leukemia (T-ALL) efficiently reduce tumor mass. Nonetheless, disease relapse attributed to survival of preleukemic stem cells (pre-LSCs) is associated with poor prognosis. Herein, we provide direct evidence that pre-LSCs are much less chemosensitive to existing chemotherapy drugs than leukemic blasts because of a distinctive lower proliferative state. Improving therapies for T-ALL requires the development of strategies to target pre-LSCs that are absolutely dependent on their microenvironment...
December 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27137657/scl-tal1-in-hematopoiesis-and-cellular-reprogramming
#13
REVIEW
T Hoang, J A Lambert, R Martin
SCL, a transcription factor of the basic helix-loop-helix family, is a master regulator of hematopoiesis. Scl specifies lateral plate mesoderm to a hematopoietic fate and establishes boundaries by inhibiting the cardiac lineage. A combinatorial interaction between Scl and Vegfa/Flk1 sets in motion the first wave of primitive hematopoiesis. Subsequently, definitive hematopoietic stem cells (HSCs) emerge from the embryo proper via an endothelial-to-hematopoietic transition controlled by Runx1, acting with Scl and Gata2...
2016: Current Topics in Developmental Biology
https://www.readbyqxmd.com/read/27009839/lmo1-gene-polymorphisms-contribute-to-decreased-neuroblastoma-susceptibility-in-a-southern-chinese-population
#14
Jing He, Wei Zhong, Jixiao Zeng, Jinhong Zhu, Ruizhong Zhang, Fenghua Wang, Tianyou Yang, Yan Zou, Huimin Xia
Neuroblastoma is one of the most commonly diagnosed extracranial solid tumors in infancy; however, the etiology of neuroblastoma remains largely unknown. Previous genome-wide association study (GWAS) indicated that several common genetic variations (rs110419 A > G, rs4758051 G > A, rs10840002 A > G and rs204938 A > G) in the LIM domain only 1 (LMO1) gene were associated with neuroblastoma susceptibility. The aim of this study was to evaluate the correlation between the four GWAS-identified LMO1 gene polymorphisms and neuroblastoma risk in a Southern Chinese population...
April 19, 2016: Oncotarget
https://www.readbyqxmd.com/read/26783042/-corrigendum-upregulated-lmo1-in-prostate-cancer-acts-as-a-novel-coactivator-of-the-androgen-receptor
#15
Hui Gu, Tong Liu, Xinze Cai, Yuxin Tong, Yan Li, Chunyu Wang, Feng Li
After the publication of the article, the authors decided to add the following grants in the Acknowledgements section: This study was supported by grants from the National Natural Science Foundation of China (Nos. 81302221, 90813038, 31371424, 31171360 and 81372337), and Natural Science Foundation of Liaoning Province, China (No. 2013021090). [the original article was published in the International Journal of Oncology 47: 2181-2187, 2015; DOI: 10.3892/ijo.2015.3195].
March 2016: International Journal of Oncology
https://www.readbyqxmd.com/read/26586772/a-polymorphism-in-the-lmo1-super-enhancer-mediates-neuroblastoma-risk
#16
(no author information available yet)
A polymorphism in the LMO1 super-enhancer protects against neuroblastoma.
January 2016: Cancer Discovery
https://www.readbyqxmd.com/read/26560027/genetic-predisposition-to-neuroblastoma-mediated-by-a-lmo1-super-enhancer-polymorphism
#17
Derek A Oldridge, Andrew C Wood, Nina Weichert-Leahey, Ian Crimmins, Robyn Sussman, Cynthia Winter, Lee D McDaniel, Maura Diamond, Lori S Hart, Shizhen Zhu, Adam D Durbin, Brian J Abraham, Lars Anders, Lifeng Tian, Shile Zhang, Jun S Wei, Javed Khan, Kelli Bramlett, Nazneen Rahman, Mario Capasso, Achille Iolascon, Daniela S Gerhard, Jaime M Guidry Auvil, Richard A Young, Hakon Hakonarson, Sharon J Diskin, A Thomas Look, John M Maris
Neuroblastoma is a paediatric malignancy that typically arises in early childhood, and is derived from the developing sympathetic nervous system. Clinical phenotypes range from localized tumours with excellent outcomes to widely metastatic disease in which long-term survival is approximately 40% despite intensive therapy. A previous genome-wide association study identified common polymorphisms at the LMO1 gene locus that are highly associated with neuroblastoma susceptibility and oncogenic addiction to LMO1 in the tumour cells...
December 17, 2015: Nature
https://www.readbyqxmd.com/read/26459575/upregulated-lmo1-in-prostate-cancer-acts-as-a-novel-coactivator-of-the-androgen-receptor
#18
Hui Gu, Tong Liu, Xinze Cai, Yuxin Tong, Yan Li, Chunyu Wang, Feng Li
LMO1, a nuclear transcription coregulator, is implicated in the pathogenesis of T-cell acute lymphoblastic leukemia and neuroblastoma. However, the role of LMO1 in human prostate cancer (PCa) is still unknown. Androgen receptor (AR) plays a critical role in the progression of prostate cancer. The activation of AR signaling pathway could be modulated by AR cofactors. In the present study, we discovered that LMO1 could bind to AR and co-localize with AR in the nucleus. In addition, the expression of LMO1 in human PCa tissues was significantly higher than that in benign prostate hyperplasia (BPH) tissues...
December 2015: International Journal of Oncology
https://www.readbyqxmd.com/read/26030754/candidate-gene-association-analysis-of-neuroblastoma-in-chinese-children-strengthens-the-role-of-lmo1
#19
Jie Lu, Ping Chu, Huanmin Wang, Yaqiong Jin, Shujing Han, Wei Han, Jun Tai, Yongli Guo, Xin Ni
Neuroblastoma (NB) is the most common extra-cranial solid tumor in children and the most frequently diagnosed cancer in the first year of life. Previous genome-wide association studies (GWAS) of Caucasian and African populations have shown that common single nucleotide polymorphisms (SNPs) in several genes are associated with the risk of developing NB, while few studies have been performed on Chinese children. Herein, we examined the association between the genetic polymorphisms in candidate genes and the risk of NB in Chinese children...
2015: PloS One
https://www.readbyqxmd.com/read/25598154/identification-of-dck1-and-lmo1-as-upstream-regulators-of-the-small-gtpase-rho5-in-saccharomyces-cerevisiae
#20
Hans-Peter Schmitz, Arne Jendretzki, Janina Wittland, Johanna Wiechert, Jürgen J Heinisch
The exact function and regulation of the small GTPase Rho5, a putative homolog of mammalian Rac1, in the yeast Saccharomyces cerevisiae have not yet been elucidated. In a genetic screen initially designed to identify novel regulators of cell wall integrity signaling, we identified the homologs of mammalian DOCK1 (Dck1) and ELMO (Lmo1) as upstream components which regulate Rho5. Deletion mutants in any of the encoding genes (DCK1, LMO1, RHO5) showed hyper-resistance to cell wall stress agents, demonstrating a function in cell wall integrity signaling...
April 2015: Molecular Microbiology
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