Gene Expression Profiling Identifies WNT7A As a Possible Candidate Gene for Decreased Cancer Risk in Fragile X Syndrome Patients

Rosales-Reynoso, Mónica Alejandra; Ochoa-Hernández, Alejandra Berenice; Aguilar‐Lemarroy, Adriana; Jave‐Suárez, Luis Felipe; Troyo-Sanromán, Rogelio; Barros‐Núñez, Patricio

doi:10.1016/j.arcmed.2010.03.001

Cited by 25 publications

(22 citation statements)

References 50 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Rosales-Reynoso and colleagues reported significant down regulation of Rad9A transcript, a DNA repair/cell cycle check point protein within the ATR/ATM DNA repair pathway, and up regulation of MSH6 (DNA mismatch repair binding protein) in patients with FXS [15]. A decrease in Rad9A transcripts could significantly impair DNA repair/replication pathway which could lead to repeat expansion.…”

Section: Resultsmentioning

confidence: 99%

“…Second, gene expression related to DNA repair/replication pathways were also assessed using data from our collaborators. Recently, Rosales-Reynoso and colleagues published a gene expression profiling study of the total peripheral blood from 10 male patients with FXS and 10 controls [15]. Two-color Human Genome Microarray (MWG Biotech H10K_DB) from the Physiology Laboratory of the Universidad Nacional Autónoma de México (http://microarrays.ifc.unam.mx) was used for this study.…”

Section: Methodsmentioning

confidence: 99%

“…Signal quantification and normalization were determined using the Array-Pro Analyzer 4.0 software for microarray images (Media Cybernetics, L.P., Silver Spring, MD). Details about the experiment protocol have been described previously [15]. Probes corresponding to the compiled list of genes in DNA repair/replication pathways were extracted from the dataset.…”

Section: Methodsmentioning

confidence: 99%

“…Corroborating evidence of haploinsufficient expression of DNA repair/replication protein transcripts has not been reported in humans. Recently, expression analysis of transcripts has occurred in patients with FXS [15-18]. We used two datasets to determine if expression transcripts of DNA repair/replication enzymes were significantly altered in patients with FXS compared to controls.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

DNA repair/replication transcripts are down regulated in patients with Fragile X Syndrome

Rosales-Reynoso

Barros‐Núñez

et al. 2013

BMC Res Notes

Self Cite

View full text Add to dashboard Cite

BackgroundFragile X Syndrome (FXS) and its associated disorders are caused by the expansion of the CGG repeat in the 5’ untranslated region of the fragile X mental retardation 1 (FMR1) gene, with disease classification based on the number of CGG repeats. The mechanisms of repeat expansion are dependent on the presence of cis elements and the absence of trans factors both of which are not mutually exclusive and contribute to repeat instability. Expansions associated with trans factors are due to the haploinsuffient or reduced expression of several DNA repair/metabolizing proteins. The reduction of expression in trans factors has been primarily conducted in animal models without substantial examination of many of these expansion mechanisms and trans factors in humans.ResultsTo understand the trans factors and pathways associated with trinucleotide repeat expansion we have analyzed two microarray datasets which characterized the transcript expression in patients with FXS and in controls.ConclusionWe observed significant down regulation of DNA damage/repair pathway transcripts. This observation was consistent in both datasets, which used different populations. Within these datasets, several transcripts overlapped in the direction of association and fold change. Further characterization of these genes will be critical to understand their role in trinucleotide repeat instability in FXS.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

DNA repair/replication transcripts are down regulated in patients with Fragile X Syndrome

Rosales-Reynoso

Barros‐Núñez

et al. 2013

BMC Res Notes

Self Cite

View full text Add to dashboard Cite

show abstract

“…In addition, the reduced Ras-PI3K/PKB signal transduction can account for several characteristics of the fragile X syndrome, including spine abnormality (Govek et al 2005;Chen et al 2010) and facial dysmorphism (O'Donnell and Warren 2002;Schubbert et al 2007). Given the hyperactivation of Ras-PI3K/PKB signaling as the primary cause of cancer (Hanahan and Weinberg 2000), the reduced maximal PI3K/PKB signaling can also account for the reduced incidence of cancer in fragile X patients (SchultzPedersen et al 2001;Rosales-Reynoso et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Pharmacological rescue of Ras signaling, GluA1-dependent synaptic plasticity, and learning deficits in a fragile X model

et al. 2014

View full text Add to dashboard Cite

Fragile X syndrome, caused by the loss of Fmr1 gene function, is the most common form of inherited mental retardation, with no effective treatment. Using a tractable animal model, we investigated mechanisms of action of a few FDA-approved psychoactive drugs that modestly benefit the cognitive performance in fragile X patients. Here we report that compounds activating serotonin (5HT) subtype 2B receptors (5HT 2B -Rs) or dopamine (DA) subtype 1-like receptors (D 1 -Rs) and/or those inhibiting 5HT 2A -Rs or D 2 -Rs moderately enhance Ras-PI3K/PKB signaling input, GluA1-dependent synaptic plasticity, and learning in Fmr1 knockout mice. Unexpectedly, combinations of these 5HT and DA compounds at low doses synergistically stimulate Ras-PI3K/PKB signal transduction and GluA1-dependent synaptic plasticity and remarkably restore normal learning in Fmr1 knockout mice without causing anxiety-related side effects. These findings suggest that properly dosed and combined FDAapproved psychoactive drugs may effectively treat the cognitive impairment associated with fragile X syndrome.

show abstract

Autism and cancer risk

Crespi

2011

Autism Research

View full text Add to dashboard Cite

A literature review was conducted on the genetic and developmental bases of autism in relation to genes and pathways associated with cancer risk. Convergent lines of evidence from four types of analysis: (1) recent theoretical studies on the causes of autism, (2) epidemiological studies, (3) genetic analyses linking autism with mutations in tumor suppressor genes and other cancer-associated genes and pathways, and (4) contrasts with schizophrenia, Parkinson's, and Alzheimer's disease indicate that autism may involve altered cancer risk. This evidence should motivate further epidemiological studies, and it provides useful insights into the nature of the genetic, epigenetic, and environmental factors underlying the etiologies of autism, other neurological conditions, and carcinogenesis.

show abstract

Gene Expression Profiling Identifies WNT7A As a Possible Candidate Gene for Decreased Cancer Risk in Fragile X Syndrome Patients

Cited by 25 publications

References 50 publications

DNA repair/replication transcripts are down regulated in patients with Fragile X Syndrome

DNA repair/replication transcripts are down regulated in patients with Fragile X Syndrome

Pharmacological rescue of Ras signaling, GluA1-dependent synaptic plasticity, and learning deficits in a fragile X model

Autism and cancer risk

Contact Info

Product

Resources

About