Angeloni D, Danilkovitch-Miagkova A, Ivanov S V, Breathnach R, Johnson B E, Leonard E J, Lerman M I
Laboratory of Immunobiology, National Cancer Institute, Frederick Cancer Research and Development Center, Frederick, Maryland.
Genes Chromosomes Cancer. 2000 Oct;29(2):147-56.
The human RON gene (MST1R) maps to 3p21.3, a region frequently altered in lung cancer and other malignancies. It encodes a receptor tyrosine kinase (RTK) closely related to MET, whose mutations are associated with neoplasia. We investigated whether RON might be involved in the development or progression of lung cancer. We first determined the exon-intron structure of the gene by direct sequencing of RON cosmid DNA and PCR products containing intronic sequences, and then developed primers suitable for mutation analysis by the single-strand conformation polymorphism (SSCP) method. Twenty coding exons were characterized, all but the first one small (average size: 170 bp), a feature shared with other RTK genes. We performed SSCP analysis of RON in small and non-small cell lung cancer samples, upon detection of its expression in a sample of lung cancer cell lines. A mutation (T915C: L296P) was found in an adenocarcinoma specimen. Several single nucleotide polymorphisms were also found. The panel of intron-anchored primers developed in this work will be useful for mutation analysis of the RON gene in different types of human tumors.
人类RON基因（MST1R）定位于3p21.3，该区域在肺癌和其他恶性肿瘤中经常发生改变。它编码一种与MET密切相关的受体酪氨酸激酶（RTK），其突变与肿瘤形成有关。我们研究了RON是否可能参与肺癌的发生或发展。我们首先通过对RON黏粒DNA和包含内含子序列的PCR产物进行直接测序来确定该基因的外显子-内含子结构，然后开发适用于单链构象多态性（SSCP）方法进行突变分析的引物。鉴定出20个编码外显子，除第一个外其余都很小（平均大小：170 bp），这是其他RTK基因共有的特征。在检测到其在一组肺癌细胞系样本中表达后，我们对小细胞肺癌和非小细胞肺癌样本进行了RON的SSCP分析。在一份腺癌标本中发现了一个突变（T915C：L296P）。还发现了几个单核苷酸多态性。在这项工作中开发的内含子锚定引物组将有助于对不同类型人类肿瘤中的RON基因进行突变分析。
