Greco A, Villa R, Pierotti M A
Division of Experimental Oncology A, Istituto Nazionale Tumori, Milan, Italy.
Oncogene. 1996 Dec 5;13(11):2463-6.
The NTRK1 gene encodes one of the receptors for the Nerve Growth Factors and it is located at 1q21-22. Rearrangements of NTRK1 are frequently detected in human papillary thyroid carcinoma and lead to the formation of chimeric oncogenes, similarly to what observed for the other neurotrophin receptor RET. In addition, the two receptor genes are target of point mutations associated with different human diseases. RET is affected by germ line and somatic mutations in MEN2A, MEN2B tumor syndromes and in the abnormal developmental Hirschsprung disease, whereas mutations of NTRK1 have been reported very recently in patients with congenital insensitivity to pain with anidrosis (CIPA). With the aim to provide a tool for searching mutations along the whole NTRK1 gene, we have determined its genomic organization. Our results demonstrated that NTRK1 is contained within 25 Kb of DNA and is organized in 17 exons, one of which is alternatively spliced. The sequence of the 5' flanking region indicates a high content in C/G, the absence of TATA box, the presence of several putative binding sites for Sp1, AP1, AP2, AP3, ATF and GCF transcription factors.
NTRK1基因编码神经生长因子的一种受体，定位于1q21 - 22。NTRK1的重排经常在人甲状腺乳头状癌中被检测到，并导致嵌合癌基因的形成，这与其他神经营养因子受体RET的情况类似。此外，这两个受体基因是与不同人类疾病相关的点突变的靶点。RET在MEN2A、MEN2B肿瘤综合征以及发育异常的先天性巨结肠疾病中受到种系和体细胞突变的影响，而NTRK1的突变最近在先天性无痛无汗症（CIPA）患者中被报道。为了提供一种在整个NTRK1基因中搜索突变的工具，我们确定了它的基因组结构。我们的结果表明，NTRK1包含在25 Kb的DNA中，由17个外显子组成，其中一个是可变剪接的。5'侧翼区域的序列表明C/G含量高，没有TATA盒，存在几个Sp1、AP1、AP2、AP3、ATF和GCF转录因子的假定结合位点。
