title: Infrequent detection of germline allele-specific expression of TGFBR1 in lymphoblasts and tissues of colon cancer patients.
abstract: Recently, germline allele-specific expression (ASE) of the gene encoding for transforming growth factor-beta type I receptor (TGFBR1) has been proposed to be a major risk factor for cancer predisposition in the colon. Germline ASE results in a lowered expression of one of the TGFBR1 alleles (>1.5-fold), and was shown to occur in approximately 20% of informative familial and sporadic colorectal cancer (CRC) cases. In the present study, using the highly quantitative pyrosequencing technique, we estimated the frequency of ASE in TGFBR1 in a cohort of affected individuals from familial clusters of advanced colon neoplasias (cancers and adenomas with high-grade dysplasia), and also from a cohort of individuals with sporadic CRCs. Cases were considered positive for the presence of ASE if demonstrating an allelic expression ratio <0.67 or >1.5. Using RNA derived from lymphoblastoid cell lines, we find that of 46 informative Caucasian advanced colon neoplasia cases with a family history, only 2 individuals display a modest ASE, with allelic ratios of 1.65 and 1.73, respectively. Given that ASE of TGFBR1, if present, would likely be more pronounced in the colon compared with other tissues, we additionally determined the allele ratios of TGFBR1 in the RNA derived from normal-appearing colonic mucosa of sporadic CRC cases. We, however, found no evidence of ASE in any of 44 informative sporadic cases analyzed. Taken together, we find that germline ASE of TGFBR1, as assayed in lymphoblastoid and colon epithelial cells of colon cancer patients, is a relatively rare event.
authors.affiliation: Department of Medicine, Ireland Cancer Center, Ohio, USA.
authors.forename: Kishore
authors.initials: K
authors.lastname: Guda
authors.forename: Leanna
authors.initials: L
authors.lastname: Natale
authors.forename: James
authors.initials: J
authors.lastname: Lutterbaugh
authors.forename: Georgia L
authors.initials: GL
authors.lastname: Wiesner
authors.forename: Susan
authors.initials: S
authors.lastname: Lewis
authors.forename: Stephan M
authors.initials: SM
authors.lastname: Tanner
authors.forename: Jerneja
authors.initials: J
authors.lastname: Tomsic
authors.forename: Laura
authors.initials: L
authors.lastname: Valle
authors.forename: Albert
authors.initials: A
authors.lastname: de la Chapelle
authors.forename: Robert C
authors.initials: RC
authors.lastname: Elston
authors.forename: Joseph
authors.initials: J
authors.lastname: Willis
authors.forename: Sanford D
authors.initials: SD
authors.lastname: Markowitz
mesh_terms: D000483:Alleles; D001483:Base Sequence; D015331:Cohort Studies; D003110:Colonic Neoplasms / Q000235:genetics* / Q000473:pathology; D017931:DNA Primers; D005854:Germ Cells; D006801:Humans; D008214:Lymphocytes / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics*
chemical_list: D017931:DNA Primers; D018125:Receptors, Transforming Growth Factor beta; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625841:TGFBR1 protein, human