title: Type I transforming growth factor beta receptor maps to 9q22 and exhibits a polymorphism and a rare variant within a polyalanine tract.
abstract: In a search for mutations of the type I transforming growth factor beta receptor (TbetaR-I), we mapped the gene to 9q22 and found a common polymorphism [TbetaR-I(6A)] and a rare variant [TbetaR-I(10A)] of TbetaR-I, causing an in-frame deletion of three alanines and an in-frame insertion of one alanine, respectively, in the receptor's extracellular domain. The biological relevance of the polymorphism TbetaR-I(6A) was investigated. When TbetaR-I(6A) was transiently transfected into TbetaR-I-deficient cells, the growth-inhibitory effects of transforming growth factor beta were restored. TbetaR-I(6A) and TbetaR-I(10A) frequency were assessed in 108 tumor samples and 80 nontumor samples from patients with a diagnosis of cancer, as well as in 118 normal blood donors of comparable ethnic composition. The frequency of TbetaR-I(6A) heterozygotes was fairly similar in normal blood donors (8%), in nontumor DNA of patients with a diagnosis of cancer (10%), and in tumor samples (14%). However, the frequency of TbetaR-I(6A) homozygotes among nontumor (4%) and tumor (8%) samples obtained from patients with a diagnosis of cancer was higher than that predicted by the Hardy-Weinberg law. The clinical and biological significance of TbetaR-I(6A) homozygosity needs to be further investigated.
authors.affiliation: Department of Medicine, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
authors.forename: B
authors.initials: B
authors.lastname: Pasche
authors.forename: Y
authors.initials: Y
authors.lastname: Luo
authors.forename: P H
authors.initials: PH
authors.lastname: Rao
authors.forename: S D
authors.initials: SD
authors.lastname: Nimer
authors.forename: E
authors.initials: E
authors.lastname: Dmitrovsky
authors.forename: P
authors.initials: P
authors.lastname: Caron
authors.forename: L
authors.initials: L
authors.lastname: Luzzatto
authors.forename: K
authors.initials: K
authors.lastname: Offit
authors.forename: C
authors.initials: C
authors.lastname: Cordon-Cardo
authors.forename: B
authors.initials: B
authors.lastname: Renault
authors.forename: J M
authors.initials: JM
authors.lastname: Satagopan
authors.forename: V V
authors.initials: VV
authors.lastname: Murty
authors.forename: J
authors.initials: J
authors.lastname: Massagué
mesh_terms: D000208:Acute Disease; D000409:Alanine / Q000235:genetics; D000595:Amino Acid Sequence; D001782:Blood Donors; D002874:Chromosome Mapping; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics*; D003062:Codon / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics; D006801:Humans; D007951:Leukemia, Myeloid / Q000235:genetics*; D008969:Molecular Sequence Data; D011110:Polymorphism, Genetic; D018125:Receptors, Transforming Growth Factor beta / Q000737:chemistry / Q000235:genetics*; D017384:Sequence Deletion; D001749:Urinary Bladder Neoplasms / Q000235:genetics
chemical_list: D003062:Codon; D018125:Receptors, Transforming Growth Factor beta; D000409:Alanine