Identification of novel GRM1 mutations and single nucleotide polymorphisms in prostate cancer cell lines and tissues.
Metabotropic glutamate receptor 1 (GRM1) signaling has been implicated in benign and malignant disorders including prostate cancer (PCa). To further explore the role of genetic alterations of GRM1 in PCa, we screened the entire human GRM1 gene including coding sequence, exon-intron junctions, and fl...
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doaj-5b2a9a62c6644e82b0c7fce0a0bea36c2020-11-25T02:42:40ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0197e10320410.1371/journal.pone.0103204Identification of novel GRM1 mutations and single nucleotide polymorphisms in prostate cancer cell lines and tissues.Shafat AliMojgan ShouridehShahriar KoochekpourMetabotropic glutamate receptor 1 (GRM1) signaling has been implicated in benign and malignant disorders including prostate cancer (PCa). To further explore the role of genetic alterations of GRM1 in PCa, we screened the entire human GRM1 gene including coding sequence, exon-intron junctions, and flanking untranslated regions (UTRs) for the presence of mutations and single nucleotide polymorphisms (SNPs) in several PCa cell lines and matched tumor-normal tissues from Caucasian Americans (CAs) and African Americans (AAs). We used bidirectional sequencing, allele-specific PCR, and bioinformatics to identify the genetic changes in GRM1 and to predict their functional role. A novel missense mutation identified at C1744T (582 Pro > Ser) position of GRM1 gene in a primary AA-PCa cell line (E006AA) was predicted to affect the protein stability and functions. Another novel mutation identified at exon-intron junction of exon-8 in C4-2B cell line resulted in alteration of the GRM1 splicing donor site. In addition, we found missense SNP at T2977C (993 Ser > Pro) position and multiple non-coding mutations and SNPs in 3'-UTR of GRM1 gene in PCa cell lines and tissues. These novel mutations may contribute to the disease by alterations in GRM1 gene splicing, receptor activation, and post-receptor downstream signaling.http://europepmc.org/articles/PMC4111546?pdf=render |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shafat Ali Mojgan Shourideh Shahriar Koochekpour |
spellingShingle |
Shafat Ali Mojgan Shourideh Shahriar Koochekpour Identification of novel GRM1 mutations and single nucleotide polymorphisms in prostate cancer cell lines and tissues. PLoS ONE |
author_facet |
Shafat Ali Mojgan Shourideh Shahriar Koochekpour |
author_sort |
Shafat Ali |
title |
Identification of novel GRM1 mutations and single nucleotide polymorphisms in prostate cancer cell lines and tissues. |
title_short |
Identification of novel GRM1 mutations and single nucleotide polymorphisms in prostate cancer cell lines and tissues. |
title_full |
Identification of novel GRM1 mutations and single nucleotide polymorphisms in prostate cancer cell lines and tissues. |
title_fullStr |
Identification of novel GRM1 mutations and single nucleotide polymorphisms in prostate cancer cell lines and tissues. |
title_full_unstemmed |
Identification of novel GRM1 mutations and single nucleotide polymorphisms in prostate cancer cell lines and tissues. |
title_sort |
identification of novel grm1 mutations and single nucleotide polymorphisms in prostate cancer cell lines and tissues. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2014-01-01 |
description |
Metabotropic glutamate receptor 1 (GRM1) signaling has been implicated in benign and malignant disorders including prostate cancer (PCa). To further explore the role of genetic alterations of GRM1 in PCa, we screened the entire human GRM1 gene including coding sequence, exon-intron junctions, and flanking untranslated regions (UTRs) for the presence of mutations and single nucleotide polymorphisms (SNPs) in several PCa cell lines and matched tumor-normal tissues from Caucasian Americans (CAs) and African Americans (AAs). We used bidirectional sequencing, allele-specific PCR, and bioinformatics to identify the genetic changes in GRM1 and to predict their functional role. A novel missense mutation identified at C1744T (582 Pro > Ser) position of GRM1 gene in a primary AA-PCa cell line (E006AA) was predicted to affect the protein stability and functions. Another novel mutation identified at exon-intron junction of exon-8 in C4-2B cell line resulted in alteration of the GRM1 splicing donor site. In addition, we found missense SNP at T2977C (993 Ser > Pro) position and multiple non-coding mutations and SNPs in 3'-UTR of GRM1 gene in PCa cell lines and tissues. These novel mutations may contribute to the disease by alterations in GRM1 gene splicing, receptor activation, and post-receptor downstream signaling. |
url |
http://europepmc.org/articles/PMC4111546?pdf=render |
work_keys_str_mv |
AT shafatali identificationofnovelgrm1mutationsandsinglenucleotidepolymorphismsinprostatecancercelllinesandtissues AT mojganshourideh identificationofnovelgrm1mutationsandsinglenucleotidepolymorphismsinprostatecancercelllinesandtissues AT shahriarkoochekpour identificationofnovelgrm1mutationsandsinglenucleotidepolymorphismsinprostatecancercelllinesandtissues |
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1724772219652931584 |