Other search tools

About this data

The publication data currently available has been vetted by Vanderbilt faculty, staff, administrators and trainees. The data itself is retrieved directly from NCBI's PubMed and is automatically updated on a weekly basis to ensure accuracy and completeness.

If you have any questions or comments, please contact us.

Results: 1 to 10 of 39

Publication Record

Connections

Mutant IDH1 and seizures in patients with glioma.
Chen H, Judkins J, Thomas C, Wu M, Khoury L, Benjamin CG, Pacione D, Golfinos JG, Kumthekar P, Ghamsari F, Chen L, Lein P, Chetkovich DM, Snuderl M, Horbinski C
(2017) Neurology 88: 1805-1813
MeSH Terms: Action Potentials, Animals, Brain Neoplasms, Cells, Cultured, Cerebral Cortex, Chromosome Deletion, Chromosomes, Human, Pair 1, Female, Glioma, Glutarates, Humans, Isocitrate Dehydrogenase, Male, Middle Aged, Mutation, Neoplasm Grading, Neurons, Rats, Sprague-Dawley, Retrospective Studies, Seizures
Show Abstract · Added April 2, 2019
OBJECTIVE - Because the d-2-hydroxyglutarate (D2HG) product of mutant isocitrate dehydrogenase 1 (IDH1) is released by tumor cells into the microenvironment and is structurally similar to the excitatory neurotransmitter glutamate, we sought to determine whether IDH1 increases the risk of seizures in patients with glioma, and whether D2HG increases the electrical activity of neurons.
METHODS - Three WHO grade II-IV glioma cohorts from separate institutions (total N = 712) were retrospectively assessed for the presence of preoperative seizures and tumor location, WHO grade, 1p/19q codeletion, and IDH1 status. Rat cortical neurons were grown on microelectrode arrays, and their electrical activity was measured before and after treatment with exogenous D2HG, in the presence or absence of the selective NMDA antagonist, AP5.
RESULTS - Preoperative seizures were observed in 18%-34% of IDH1 wild-type (IDH1) patients and in 59%-74% of IDH1 patients ( < 0.001). Multivariable analysis, including WHO grade, 1p/19q codeletion, and temporal lobe location, showed that IDH1 was an independent correlate with seizures (odds ratio 2.5, 95% confidence interval 1.6-3.9, < 0.001). Exogenous D2HG increased the firing rate of cultured rat cortical neurons 4- to 6-fold, but was completely blocked by AP5.
CONCLUSIONS - The D2HG product of IDH1 may increase neuronal activity by mimicking the activity of glutamate on the NMDA receptor, and IDH1 gliomas are more likely to cause seizures in patients. This has rapid translational implications for the personalized management of tumor-associated epilepsy, as targeted IDH1 inhibitors may improve antiepileptic therapy in patients with IDH1 gliomas.
© 2017 American Academy of Neurology.
0 Communities
1 Members
0 Resources
MeSH Terms
The somatic genomic landscape of chromophobe renal cell carcinoma.
Davis CF, Ricketts CJ, Wang M, Yang L, Cherniack AD, Shen H, Buhay C, Kang H, Kim SC, Fahey CC, Hacker KE, Bhanot G, Gordenin DA, Chu A, Gunaratne PH, Biehl M, Seth S, Kaipparettu BA, Bristow CA, Donehower LA, Wallen EM, Smith AB, Tickoo SK, Tamboli P, Reuter V, Schmidt LS, Hsieh JJ, Choueiri TK, Hakimi AA, The Cancer Genome Atlas Research Network, Chin L, Meyerson M, Kucherlapati R, Park WY, Robertson AG, Laird PW, Henske EP, Kwiatkowski DJ, Park PJ, Morgan M, Shuch B, Muzny D, Wheeler DA, Linehan WM, Gibbs RA, Rathmell WK, Creighton CJ
(2014) Cancer Cell 26: 319-330
MeSH Terms: Base Sequence, Carcinoma, Renal Cell, Chromosome Breakpoints, Chromosome Deletion, Chromosomes, Human, DNA Copy Number Variations, DNA Methylation, DNA Mutational Analysis, DNA, Mitochondrial, Exome, Genome, Human, Humans, Kidney Neoplasms, Molecular Sequence Data, Promoter Regions, Genetic, Telomerase, Transcriptome
Show Abstract · Added October 17, 2015
We describe the landscape of somatic genomic alterations of 66 chromophobe renal cell carcinomas (ChRCCs) on the basis of multidimensional and comprehensive characterization, including mtDNA and whole-genome sequencing. The result is consistent that ChRCC originates from the distal nephron compared with other kidney cancers with more proximal origins. Combined mtDNA and gene expression analysis implicates changes in mitochondrial function as a component of the disease biology, while suggesting alternative roles for mtDNA mutations in cancers relying on oxidative phosphorylation. Genomic rearrangements lead to recurrent structural breakpoints within TERT promoter region, which correlates with highly elevated TERT expression and manifestation of kataegis, representing a mechanism of TERT upregulation in cancer distinct from previously observed amplifications and point mutations.
Copyright © 2014 Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
17 MeSH Terms
Methylation of promoters of microRNAs and their host genes in myelodysplastic syndromes.
Erdogan B, Bosompem A, Peng D, Han L, Smith E, Kennedy ME, Alford CE, Wu H, Zhao Z, Mosse CA, El-Rifai W, Kim AS
(2013) Leuk Lymphoma 54: 2720-7
MeSH Terms: Cell Differentiation, Cell Line, Tumor, Chromosome Deletion, Chromosome Mapping, CpG Islands, DNA Methylation, Gene Expression Regulation, Humans, MicroRNAs, Myelodysplastic Syndromes, Promoter Regions, Genetic, Transcriptome, Tretinoin
Show Abstract · Added September 3, 2013
Myelodysplastic syndromes (MDS) are a group of hematopoietic malignancies characterized by ineffective hematopoiesis. Recently, we identified MDS-associated microRNAs (miRNAs) that are down-regulated in MDS. This study examines possible explanations for that observed down-regulation of miRNA expression in MDS. Since genomic losses are insufficient to explain the down-regulation of all our MDS-associated miRNAs, we explored other avenues. We demonstrate that these miRNAs are predominantly intragenic, and that, in many cases, they and their host genes are expressed in a similar pattern during myeloid maturation, suggesting their co-regulation. This co-regulation is further supported by the down-regulation of several of the host genes in MDS and increased methylation of the shared promoters of several miRNAs and their respective host genes. These studies identify a role of hypermethylation of miRNA promoters in the down-regulation of MDS-associated miRNAs, unifying research on miRNAs in MDS and epigenetic regulation in MDS into a common pathway.
0 Communities
3 Members
0 Resources
13 MeSH Terms
CUX1 is a haploinsufficient tumor suppressor gene on chromosome 7 frequently inactivated in acute myeloid leukemia.
McNerney ME, Brown CD, Wang X, Bartom ET, Karmakar S, Bandlamudi C, Yu S, Ko J, Sandall BP, Stricker T, Anastasi J, Grossman RL, Cunningham JM, Le Beau MM, White KP
(2013) Blood 121: 975-83
MeSH Terms: Acute Disease, Animals, Blotting, Western, Cell Line, Tumor, Chromosome Deletion, Chromosomes, Human, Pair 7, Drosophila melanogaster, Gene Expression Profiling, Haploinsufficiency, HeLa Cells, Homeodomain Proteins, Humans, Interleukin Receptor Common gamma Subunit, K562 Cells, Leukemia, Myeloid, Mice, Mice, Inbred NOD, Mice, Knockout, Mice, SCID, Nuclear Proteins, RNA Interference, Repressor Proteins, Reverse Transcriptase Polymerase Chain Reaction, Translocation, Genetic, Tumor Suppressor Proteins, U937 Cells, Xenograft Model Antitumor Assays
Show Abstract · Added March 28, 2014
Loss of chromosome 7 and del(7q) [-7/del(7q)] are recurring cytogenetic abnormalities in hematologic malignancies, including acute myeloid leukemia and therapy-related myeloid neoplasms, and associated with an adverse prognosis. Despite intensive effort by many laboratories, the putative myeloid tumor suppressor(s) on chromosome 7 has not yet been identified.We performed transcriptome sequencing and SNP array analysis on de novo and therapy-related myeloid neoplasms, half with -7/del(7q). We identified a 2.17-Mb commonly deleted segment on chromosome band 7q22.1 containing CUX1, a gene encoding a homeodomain-containing transcription factor. In 1 case, CUX1 was disrupted by a translocation, resulting in a loss-of-function RNA fusion transcript. CUX1 was the most significantly differentially expressed gene within the commonly deleted segment and was expressed at haploinsufficient levels in -7/del(7q) leukemias. Haploinsufficiency of the highly conserved ortholog, cut, led to hemocyte overgrowth and tumor formation in Drosophila melanogaster. Similarly, haploinsufficiency of CUX1 gave human hematopoietic cells a significant engraftment advantage on transplantation into immunodeficient mice. Within the RNA-sequencing data, we identified a CUX1-associated cell cycle transcriptional gene signature, suggesting that CUX1 exerts tumor suppressor activity by regulating proliferative genes. These data identify CUX1 as a conserved, haploinsufficient tumor suppressor frequently deleted in myeloid neoplasms.
0 Communities
1 Members
0 Resources
27 MeSH Terms
Genomic imbalances in benign metastasizing leiomyoma: characterization by conventional karyotypic, fluorescence in situ hybridization, and whole genome SNP array analysis.
Bowen JM, Cates JM, Kash S, Itani D, Gonzalez A, Huang D, Oliveira A, Bridge JA
(2012) Cancer Genet 205: 249-54
MeSH Terms: Chromosome Deletion, Chromosomes, Human, Pair 7, Female, Gene Rearrangement, Humans, In Situ Hybridization, Fluorescence, Karyotyping, Leiomyoma, Lung Neoplasms, Middle Aged, Muscle Neoplasms, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Thigh, Uterine Neoplasms
Show Abstract · Added March 15, 2013
Benign metastasizing leiomyoma, a rare condition of controversial origin, is characterized by the occurrence of extrauterine smooth muscle tumors primarily affecting the lungs of women with a history of uterine leiomyomas. Numerous genetic studies of uterine leiomyoma with rearrangements of the HMGA2 and HMGA1 loci defined in prominent subgroups have been conducted. In contrast, cytogenetic and molecular descriptions of benign metastasizing leiomyoma are few, and, in particular, this entity has not been previously subjected to single nucleotide polymorphism (SNP) array analysis. In this study, conventional karyotypic, and/or molecular cytogenetic, and SNP array characterization of a pleuropulmonary benign mestasizing leiomyoma and a synchronous deep soft tissue leiomyoma of the thigh, which arose in a 56-year-old female with a remote history of uterine leiomyomata, revealed rearrangement of the HMGA1 (6p21) locus and nearly identical genomic profiles, including loss of chromosome 7 material in both lesions. These findings suggest that both the deep soft tissue and pleuropulmonary lesions were derived from the same abnormal clone and are genetically related to uterine leiomyomata.
Copyright © 2012 Elsevier Inc. All rights reserved.
0 Communities
1 Members
0 Resources
15 MeSH Terms
Ripply3, a Tbx1 repressor, is required for development of the pharyngeal apparatus and its derivatives in mice.
Okubo T, Kawamura A, Takahashi J, Yagi H, Morishima M, Matsuoka R, Takada S
(2011) Development 138: 339-48
MeSH Terms: Animals, Base Sequence, Branchial Region, Chromosome Deletion, Chromosomes, Human, Pair 22, DNA Primers, Female, Gene Expression Regulation, Developmental, Heart Defects, Congenital, Humans, Male, Mice, Mice, 129 Strain, Mice, Inbred C57BL, Mice, Knockout, Paired Box Transcription Factors, Phenotype, Pregnancy, Repressor Proteins, T-Box Domain Proteins
Show Abstract · Added December 9, 2016
The pharyngeal apparatus is a transient structure that gives rise to the thymus and the parathyroid glands and also contributes to the development of arteries and the cardiac outflow tract. A typical developmental disorder of the pharyngeal apparatus is the 22q11 deletion syndrome (22q11DS), for which Tbx1 is responsible. Here, we show that Ripply3 can modulate Tbx1 activity and plays a role in the development of the pharyngeal apparatus. Ripply3 expression is observed in the pharyngeal ectoderm and endoderm and overlaps with strong expression of Tbx1 in the caudal pharyngeal endoderm. Ripply3 suppresses transcriptional activation by Tbx1 in luciferase assays in vitro. Ripply3-deficient mice exhibit abnormal development of pharyngeal derivatives, including ectopic formation of the thymus and the parathyroid gland, as well as cardiovascular malformation. Corresponding with these defects, Ripply3-deficient embryos show hypotrophy of the caudal pharyngeal apparatus. Ripply3 represses Tbx1-induced expression of Pax9 in luciferase assays in vitro, and Ripply3-deficient embryos exhibit upregulated Pax9 expression. Together, our results show that Ripply3 plays a role in pharyngeal development, probably by regulating Tbx1 activity.
0 Communities
0 Members
1 Resources
20 MeSH Terms
Genome-wide analysis of copy number variation in type 1 diabetes.
Grayson BL, Smith ME, Thomas JW, Wang L, Dexheimer P, Jeffrey J, Fain PR, Nanduri P, Eisenbarth GS, Aune TM
(2010) PLoS One 5: e15393
MeSH Terms: Adult, Chromosome Deletion, Chromosomes, Human, Pair 13, Chromosomes, Human, Pair 2, Chromosomes, Human, Pair 6, Chromosomes, Human, Pair 7, Chromosomes, Human, Pair 8, Cohort Studies, DNA Copy Number Variations, Diabetes Mellitus, Type 1, Gene Deletion, Gene Frequency, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Humans, Oligonucleotide Array Sequence Analysis, Polymorphism, Single Nucleotide, Risk Factors, Twins, Monozygotic
Show Abstract · Added December 10, 2013
Type 1 diabetes (T1D) tends to cluster in families, suggesting there may be a genetic component predisposing to disease. However, a recent large-scale genome-wide association study concluded that identified genetic factors, single nucleotide polymorphisms, do not account for overall familiality. Another class of genetic variation is the amplification or deletion of >1 kilobase segments of the genome, also termed copy number variations (CNVs). We performed genome-wide CNV analysis on a cohort of 20 unrelated adults with T1D and a control (Ctrl) cohort of 20 subjects using the Affymetrix SNP Array 6.0 in combination with the Birdsuite copy number calling software. We identified 39 CNVs as enriched or depleted in T1D versus Ctrl. Additionally, we performed CNV analysis in a group of 10 monozygotic twin pairs discordant for T1D. Eleven of these 39 CNVs were also respectively enriched or depleted in the Twin cohort, suggesting that these variants may be involved in the development of islet autoimmunity, as the presently unaffected twin is at high risk for developing islet autoimmunity and T1D in his or her lifetime. These CNVs include a deletion on chromosome 6p21, near an HLA-DQ allele. CNVs were found that were both enriched or depleted in patients with or at high risk for developing T1D. These regions may represent genetic variants contributing to development of islet autoimmunity in T1D.
1 Communities
1 Members
0 Resources
20 MeSH Terms
Rare familial 16q21 microdeletions under a linkage peak implicate cadherin 8 (CDH8) in susceptibility to autism and learning disability.
Pagnamenta AT, Khan H, Walker S, Gerrelli D, Wing K, Bonaglia MC, Giorda R, Berney T, Mani E, Molteni M, Pinto D, Le Couteur A, Hallmayer J, Sutcliffe JS, Szatmari P, Paterson AD, Scherer SW, Vieland VJ, Monaco AP
(2011) J Med Genet 48: 48-54
MeSH Terms: Adolescent, Autistic Disorder, Base Sequence, Cadherins, Child, Chromosome Deletion, Chromosomes, Human, Pair 16, DNA Copy Number Variations, DNA Mutational Analysis, Family, Female, Gene Expression Regulation, Genetic Linkage, Genetic Predisposition to Disease, Genome, Human, Humans, Intelligence Tests, Internet, Learning Disorders, Male, Molecular Sequence Data, Pedigree, Young Adult
Show Abstract · Added February 20, 2014
BACKGROUND - Autism spectrum disorder (ASD) is characterised by impairments in social communication and by a pattern of repetitive behaviours, with learning disability (LD) typically seen in up to 70% of cases. A recent study using the PPL statistical framework identified a novel region of genetic linkage on chromosome 16q21 that is limited to ASD families with LD.
METHODS - In this study, two families with autism and/or LD are described which harbour rare >1.6 Mb microdeletions located within this linkage region. The deletion breakpoints are mapped at base-pair resolution and segregation analysis is performed using a combination of 1M single nucleotide polymorphism (SNP) technology, array comparative genomic hybridisation (CGH), long-range PCR, and Sanger sequencing. The frequency of similar genomic variants in control subjects is determined through analysis of published SNP array data. Expression of CDH8, the only gene disrupted by these microdeletions, is assessed using reverse transcriptase PCR and in situ hybridisation analysis of 9 week human embryos.
RESULTS - The deletion of chr16: 60 025 584-61 667 839 was transmitted to three of three boys with autism and LD and none of four unaffected siblings, from their unaffected mother. In a second family, an overlapping deletion of chr16: 58 724 527-60 547 472 was transmitted to an individual with severe LD from his father with moderate LD. No copy number variations (CNVs) disrupting CDH8 were observed in 5023 controls. Expression analysis indicates that the two CDH8 isoforms are present in the developing human cortex.
CONCLUSION - Rare familial 16q21 microdeletions and expression analysis implicate CDH8 in susceptibility to autism and LD.
0 Communities
1 Members
0 Resources
23 MeSH Terms
Somatic chromosome abnormalities in the lungs of patients with pulmonary arterial hypertension.
Aldred MA, Comhair SA, Varella-Garcia M, Asosingh K, Xu W, Noon GP, Thistlethwaite PA, Tuder RM, Erzurum SC, Geraci MW, Coldren CD
(2010) Am J Respir Crit Care Med 182: 1153-60
MeSH Terms: Adult, Airway Remodeling, Bone Morphogenetic Protein Receptors, Type II, Cell Proliferation, Child, Chromosome Aberrations, Chromosome Deletion, DNA Copy Number Variations, Endothelial Cells, Female, Gene Rearrangement, Genome-Wide Association Study, Genomic Instability, Germ-Line Mutation, Humans, Hypertension, Pulmonary, In Situ Hybridization, Fluorescence, Lung, Microarray Analysis, Middle Aged, Myocytes, Smooth Muscle, Polymorphism, Single Nucleotide, Pulmonary Artery, Pulmonary Disease, Chronic Obstructive, X Chromosome Inactivation
Show Abstract · Added November 17, 2011
RATIONALE - Vascular remodeling in pulmonary arterial hypertension (PAH) involves proliferation and migration of endothelial and smooth muscle cells, leading to obliterative vascular lesions. Previous studies have indicated that the endothelial cell proliferation is quasineoplastic, with evidence of monoclonality and instability of short DNA microsatellite sequences.
OBJECTIVES - To assess whether there is larger-scale genomic instability.
METHODS - We performed genome-wide microarray copy number analysis on pulmonary artery endothelial cells and smooth muscle cells isolated from the lungs of patients with PAH.
MEASUREMENTS AND MAIN RESULTS - Mosaic chromosomal abnormalities were detected in PAEC cultures from five of nine PAH lungs but not in normal (n = 8) or disease control subjects (n = 5). Fluorescent in situ hybridization analysis confirmed the presence of these abnormalities in vivo in two of three cases. One patient harbored a germline mutation of BMPR2, the primary genetic cause of PAH, and somatic loss of chromosome-13, which constitutes a second hit in the same pathway by deleting Smad-8. In two female subjects with mosaic loss of the X chromosome, methylation analysis showed that the active X was deleted. One subject also showed completely skewed X-inactivation in the nondeleted cells, suggesting the pulmonary artery endothelial cell population was clonal before the acquisition of the chromosome abnormality.
CONCLUSIONS - Our data indicate a high frequency of genetically abnormal subclones within PAH lung vessels and provide the first definitive evidence of a second genetic hit in a patient with a germline BMPR2 mutation. We propose that these chromosome abnormalities may confer a growth advantage and thus contribute to the progression of PAH.
0 Communities
1 Members
0 Resources
25 MeSH Terms
Loss of Phosphatase and Tensin homologue deleted on chromosome 10 engages ErbB3 and insulin-like growth factor-I receptor signaling to promote antiestrogen resistance in breast cancer.
Miller TW, Pérez-Torres M, Narasanna A, Guix M, Stål O, Pérez-Tenorio G, Gonzalez-Angulo AM, Hennessy BT, Mills GB, Kennedy JP, Lindsley CW, Arteaga CL
(2009) Cancer Res 69: 4192-201
MeSH Terms: Breast Neoplasms, Cell Division, Cell Line, Tumor, Chromosome Deletion, Chromosomes, Human, Pair 19, Drug Resistance, Neoplasm, Estrogen Receptor Modulators, Female, Genes, Reporter, Humans, PTEN Phosphohydrolase, Receptor, ErbB-2, Receptor, ErbB-3, Receptor, IGF Type 1, Transcription, Genetic
Show Abstract · Added March 5, 2014
Knockdown of the tumor suppressor phosphatase Phosphatase and tensin homologue deleted on chromosome 10 (PTEN) with shRNA in three estrogen receptor (ER)-positive breast cancer cell lines resulted in increased phosphatidylinositol-3 kinase (PI3K) and AKT activities, resistance to tamoxifen and fulvestrant, and hormone-independent growth. PTEN knockdown induced the up-regulation of ER transcriptional activity in MCF-7 cells but decreased ER protein levels and transcriptional activity in T47D and MDA-361 cells. Tamoxifen and fulvestrant treatment inhibited estradiol-induced ER transcriptional activity in all shPTEN cell lines but did not abrogate the increased cell proliferation induced by PTEN knockdown. PTEN knockdown increased basal and ligand-induced activation of the insulin-like growth factor-I (IGF-I) and ErbB3 receptor tyrosine kinases, and prolonged the association of the p85 PI3K subunit with the IGF-I receptor (IGF-IR) effector insulin receptor substrate-1 and with ErbB3, implicating PTEN in the modulation of signaling upstream of PI3K. Consistent with these data, PTEN levels inversely correlated with levels of tyrosine-phosphorylated IGF-IR in tissue lysate arrays of primary breast cancers. Inhibition of IGF-IR and/or ErbB2-mediated activation of ErbB3 with tyrosine kinase inhibitors restored hormone dependence and the growth inhibitory effect of tamoxifen and fulvestrant on shPTEN cells, suggesting that cotargeting both ER and receptor tyrosine kinase pathways holds promise for the treatment of patients with ER+, PTEN-deficient breast cancers.
1 Communities
2 Members
0 Resources
15 MeSH Terms