Infrequent detection of germline allele-specific expression of TGFBR1 in lymphoblasts and tissues of colon cancer patients.

Hdl Handle:
http://hdl.handle.net/10147/94478
Title:
Infrequent detection of germline allele-specific expression of TGFBR1 in lymphoblasts and tissues of colon cancer patients.
Authors:
Guda, Kishore; Natale, Leanna; Lutterbaugh, James; Wiesner, Georgia L; Lewis, Susan; Tanner, Stephan M; Tomsic, Jerneja; Valle, Laura; de la Chapelle, Albert; Elston, Robert C; Willis, Joseph; Markowitz, Sanford D
Affiliation:
Department of Medicine, Ireland Cancer Center, Ohio, USA.
Citation:
Infrequent detection of germline allele-specific expression of TGFBR1 in lymphoblasts and tissues of colon cancer patients. 2009, 69 (12):4959-61 Cancer Res.
Journal:
Cancer research
Issue Date:
15-Jun-2009
URI:
http://hdl.handle.net/10147/94478
DOI:
10.1158/0008-5472.CAN-09-0225
PubMed ID:
19509225
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.
Language:
en
Keywords:
COLORECTAL CANCER
MeSH:
Alleles; Base Sequence; Cohort Studies; Colonic Neoplasms; DNA Primers; Germ Cells; Humans; Lymphocytes; Polymerase Chain Reaction; Protein-Serine-Threonine Kinases; Receptors, Transforming Growth Factor beta
ISSN:
1538-7445

Full metadata record

DC FieldValue Language
dc.contributor.authorGuda, Kishoreen
dc.contributor.authorNatale, Leannaen
dc.contributor.authorLutterbaugh, Jamesen
dc.contributor.authorWiesner, Georgia Len
dc.contributor.authorLewis, Susanen
dc.contributor.authorTanner, Stephan Men
dc.contributor.authorTomsic, Jernejaen
dc.contributor.authorValle, Lauraen
dc.contributor.authorde la Chapelle, Alberten
dc.contributor.authorElston, Robert Cen
dc.contributor.authorWillis, Josephen
dc.contributor.authorMarkowitz, Sanford Den
dc.date.accessioned2010-03-18T10:57:35Z-
dc.date.available2010-03-18T10:57:35Z-
dc.date.issued2009-06-15-
dc.identifier.citationInfrequent detection of germline allele-specific expression of TGFBR1 in lymphoblasts and tissues of colon cancer patients. 2009, 69 (12):4959-61 Cancer Res.en
dc.identifier.issn1538-7445-
dc.identifier.pmid19509225-
dc.identifier.doi10.1158/0008-5472.CAN-09-0225-
dc.identifier.urihttp://hdl.handle.net/10147/94478-
dc.description.abstractRecently, 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.-
dc.language.isoenen
dc.subjectCOLORECTAL CANCERen
dc.subject.meshAlleles-
dc.subject.meshBase Sequence-
dc.subject.meshCohort Studies-
dc.subject.meshColonic Neoplasms-
dc.subject.meshDNA Primers-
dc.subject.meshGerm Cells-
dc.subject.meshHumans-
dc.subject.meshLymphocytes-
dc.subject.meshPolymerase Chain Reaction-
dc.subject.meshProtein-Serine-Threonine Kinases-
dc.subject.meshReceptors, Transforming Growth Factor beta-
dc.titleInfrequent detection of germline allele-specific expression of TGFBR1 in lymphoblasts and tissues of colon cancer patients.en
dc.contributor.departmentDepartment of Medicine, Ireland Cancer Center, Ohio, USA.en
dc.identifier.journalCancer researchen

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