scholarly journals Germline Allele-Specific Expression of TGFBR1 Confers an Increased Risk of Colorectal Cancer

Science ◽  
2008 ◽  
Vol 321 (5894) ◽  
pp. 1361-1365 ◽  
Author(s):  
L. Valle ◽  
T. Serena-Acedo ◽  
S. Liyanarachchi ◽  
H. Hampel ◽  
I. Comeras ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Increased Risk ◽  
Allele Specific

scholarly journals Genetic and transcriptional analysis of human host response to healthy gut microbiome

2016 ◽  
Author(s):  
Allison L. Richards ◽  
Michael B. Burns ◽  
Adnan Alazizi ◽  
Luis B. Barreiro ◽  
Roger Pique-Regi ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Gut Microbiome ◽  
Molecular Mechanisms ◽  
Transcriptional Response ◽  
Experimental System ◽  
Transcriptional Analysis ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Disease States ◽  
Allele Specific

AbstractMany studies have demonstrated the importance of the gut microbiome in healthy and disease states. However, establishing the causality of host-microbiome interactions in humans is still challenging. Here, we describe a novel experimental system to define the transcriptional response induced by the microbiome in human cells and to shed light on the molecular mechanisms underlying host-gut microbiome interactions. In primary human colonic epithelial cells, we identified over 6,000 genes that change expression at various time points following co-culturing with the gut microbiome of a healthy individual. The differentially expressed genes are enriched for genes associated with several microbiome-related diseases, such as obesity and colorectal cancer. In addition, our experimental system allowed us to identify 87 host SNPs that show allele-specific expression in 69 genes. Furthermore, for 12 SNPs in 12 different genes, allele-specific expression is conditional on the exposure to the microbiome. Of these 12 genes, eight have been associated with diseases linked to the gut microbiome, specifically colorectal cancer, obesity and type 2 diabetes. Our study demonstrates a scalable approach to study host-gut microbiome interactions and can be used to identify putative mechanisms for the interplay between host genetics and microbiome in health and disease.

APC allele-specific expression in carriers of Ashkenazi Jewish mutation I1307K

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e22181-e22181
Author(s):  
G. Capella ◽  
E. Castellsague ◽  
G. Rennert ◽  
S. Gruber
Keyword(s):  
Incomplete Penetrance ◽  
Ashkenazi Jewish ◽  
Specific Expression ◽  
Single Nucleotide ◽  
Allele Specific Expression ◽  
Increased Risk ◽  
Allele Specific ◽  
Single Nucleotide Primer Extension ◽  
Rna And Dna ◽  
Dna Mutant

e22181 Background: I1307K is a missense APC variant with incomplete penetrance that has been found in 6% of Jewish Ashkenazi population and confers a two-fold increased risk to develop multiple adenomas and colorectal tumours. It is believed that it creates a hypermutable region within the gene that leads to an accumulation of mutations. It remains unknown whether the presence of this mutation modifies APC expression. Our goal was to study whether allele-specific expression (ASE) of I1307K is present at the germline and tumoral level. Methods: Paired germline/carcinoma RNA and DNA was studied from eleven I1307K carriers. To analyze changes in the mutant/wt allelic ratio we used single nucleotide primer extension (SNuPE) for the I1307K and the rs2229992 APCcoding SNP. Fourteen controls were also analyzed. Results: No germline allele specific expression was found in I1307K carriers (range=0.954–1.173). Significant ASE was observed in 8 of the 10 carcinomas analyzed. In 4 cases the I1307K allele was overexpressed (range=2.51–9.51) and in 4 cases was underexpressed (range=0.09–0.28). Tumor ASE correlated with the DNA mutant/wt allelic dose. Conclusions: I1307K variant is not associated with allelic specific expression at the germline level. I1307K overexpression is not selected for during tumor progression. No significant financial relationships to disclose.

scholarly journals Allelic Switching of DLX5, GRB10, and SVOPL during Colorectal Cancer Tumorigenesis

2019 ◽  
Vol 2019 ◽  
pp. 1-10
Author(s):  
Arnoud Boot ◽  
Jan Oosting ◽  
Saskia Doorn ◽  
Sarah Ouahoud ◽  
Marina Ventayol Garcia ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Cell Lines ◽  
Normal Mucosa ◽  
Chromosome 7 ◽  
Specific Expression ◽  
Allele Specific Expression ◽  
Human Genes ◽  
Allele Specific ◽  
Somatic Alterations ◽  
Low Passage

Allele-specific expression (ASE) is found in approximately 20-30% of human genes. During tumorigenesis, ASE changes due to somatic alterations that change the regulatory landscape. In colorectal cancer (CRC), many chromosomes show frequent gains or losses while homozygosity of chromosome 7 is rare. We hypothesized that genes essential to survival show allele-specific expression (ASE) on both alleles of chromosome 7. Using a panel of 21 recently established low-passage CRC cell lines, we performed ASE analysis by hybridizing DNA and cDNA to Infinium HumanExome-12 v1 BeadChips containing cSNPs in 392 chromosome 7 genes. The results of this initial analysis were extended and validated in a set of 89 paired normal mucosa and CRC samples. We found that 14% of genes showed ASE in one or more cell lines and identified allelic switching of the potential cell survival genes DLX5, GRB10, and SVOPL on chromosome 7, whereby the most abundantly expressed allele in the normal tissue is the lowest expressed allele in the tumor and vice versa. We established that this allelic switch does not result from loss of imprinting. The allelic switching of SVOPL may be a result of transcriptional downregulation, while the exact mechanisms resulting in the allelic switching of DLX5 and GRB10 remain to be elucidated. In conclusion, our results show that profound changes take place in allelic transcriptional regulation during the tumorigenesis of CRC.

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