Type I transforming growth factor beta receptor maps to 9q22 and exhibits a polymorphism and a rare variant within a polyalanine tract.
Type I transforming growth factor beta receptor maps to 9q22 and exhibits a polymorphism and a rare variant within a polyalanine tract.
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发表时间：
1998-07
期刊：
影响因子：
11.2
通讯作者：
B. Pasche;Yan Luo;P. Rao;S. Nimer;E. Dmitrovsky;P. Caron;L. Luzzatto;K. Offit;C. Cordon-Cardo;B. Renault;J. Satagopan;V. Murty;J. Massagué;J. Massagué
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作者：
B. Pasche;Yan Luo;P. Rao;S. Nimer;E. Dmitrovsky;P. Caron;L. Luzzatto;K. Offit;C. Cordon-Cardo;B. Renault;J. Satagopan;V. Murty;J. Massagué;J. Massagué
在寻找I型转化生长因子β受体（TbetaR-I）的突变时，我们将该基因定位于9 q22，发现了TbetaR-I的常见多态性[TbetaR-I（6A）]和罕见变体[TbetaR-I（10A）]，分别导致受体胞外结构域中三个丙氨酸的框内缺失和一个丙氨酸的框内插入。研究了多态性TbetaR-I（6A）的生物学相关性。当TbetaR-I（6A）瞬时转染到TbetaR-I缺陷细胞中时，转化生长因子β的生长抑制作用恢复。TbetaR-I（6A）和TbetaR-I（10A）频率在108个肿瘤样本和80个非肿瘤样本中进行了评估，这些样本来自诊断为癌症的患者，以及118个具有可比种族组成的正常献血者。TbetaR-I（6A）杂合子的频率在正常献血者（8%）、诊断为癌症的患者的非肿瘤DNA（10%）和肿瘤样本（14%）中相当相似。然而，从诊断为癌症的患者中获得的非肿瘤（4%）和肿瘤（8%）样本中TbetaR-I（6A）纯合子的频率高于Hardy-Weinberg定律预测的频率。TbetaR-I（6A）纯合性的临床和生物学意义有待进一步研究。
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.