title: Identification of novel GRM1 mutations and single nucleotide polymorphisms in prostate cancer cell lines and tissues.
abstract: 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.
authors: Departments of Cancer Genetics, Center for Genetics and Pharmacology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors: Shafat
authors: S
authors: Ali
authors: Departments of Cancer Genetics, Center for Genetics and Pharmacology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors: Mojgan
authors: M
authors: Shourideh
authors: Departments of Cancer Genetics, Center for Genetics and Pharmacology, Roswell Park Cancer Institute, Buffalo, New York, United States of America; Departments of Urology, Center for Genetics and Pharmacology, Roswell Park Cancer Institute, Buffalo, New York, United States of America.
authors: Shahriar
authors: S
authors: Koochekpour
mesh_terms: D001741:Black or African American / Q000235:genetics; D000483:Alleles; D045744:Cell Line, Tumor; D004847:Epithelial Cells / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005838:Genotype; D006801:Humans; D007438:Introns / Q000235:genetics; D008297:Male; D020125:Mutation, Missense / Q000235:genetics; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000473:pathology; D018094:Receptors, Metabotropic Glutamate / Q000235:genetics*; D020506:Untranslated Regions / Q000235:genetics; D044465:White People / Q000235:genetics
chemical_list: D018094:Receptors, Metabotropic Glutamate; D020506:Untranslated Regions; C104077:metabotropic glutamate receptor type 1