公开(公告)号：US5401828A

公开(公告)日：1995-03-28

申请号：US991286

申请日：1992-12-15

申请人： Bert Vogelstein ,  Darell Bigner

发明人： Bert Vogelstein ,  Darell Bigner

IPC分类号： A61K39/395 ,  A61K38/00 ,  A61K45/00 ,  A61K47/48 ,  A61K49/00 ,  A61K51/10 ,  A61P35/00 ,  C07K7/06 ,  C07K7/08 ,  C07K14/71 ,  C07K16/00 ,  C07K16/28 ,  C12N1/21 ,  C12N5/10 ,  C12N15/02 ,  C12N15/09 ,  C12N15/12 ,  C12P21/02 ,  C12P21/08 ,  C12Q1/68 ,  G01N33/53 ,  G01N33/574 ,  G01N33/577 ,  C07K5/00 ,  C07K7/00 ,  C07K3/00 ,  C07K15/00

CPC分类号： C07K14/71 ,  A61K47/48561 ,  A61K51/103 ,  C07K16/2863 ,  C12Q1/6886 ,  A61K2123/00 ,  A61K38/00 ,  C07K2317/34 ,  C12Q2600/156 ,  Y10S435/96 ,  Y10S436/804 ,  Y10S436/813 ,  Y10S530/81 ,  Y10S530/812

摘要： The epidermal growth factor receptor (EGFR) gene is amplified in 40% of malignant gliomas and the amplified genes are frequently rearranged. The genetic alterations associated with these rearrangements are characterized in five malignant gliomas. In one tumor, the rearrangement resulted in the deletion of most of the extracytoplasmic domain of the receptor, resulting in a hybrid mRNA between new sequences and the truncated EGFR. The predicted amino acid sequence of the protein from this tumor was remarkably similar to that described for several viral erb-B oncogenes. Four other tumors were noted to have internal deletions of the EGF receptor gene. These rearrangements brought about in-frame deletions affecting either of two cysteine-rich domains in the extracytoplasmic portion of the molecule. The clonal nature of these alterations, and the fact that identical alterations were seen in more than one tumor, suggests a role for these mutant receptor proteins in tumorigenesis. Furthermore, these studies document the existence of tumor specific cell molecules resulting from somatic mutation.

摘要翻译： 在40％恶性胶质瘤中扩增表皮生长因子受体（EGFR）基因，经扩增的基因经常重排。 与这些重排相关的遗传改变的特征在于五种恶性胶质瘤。 在一个肿瘤中，重排导致大部分受体胞外结构域的缺失，导致新序列与截短的EGFR之间的杂合mRNA。 来自该肿瘤的蛋白质的预测氨基酸序列与对于几种病毒erb-B致癌基因所描述的非常相似。 注意到另外四个肿瘤具有EGF受体基因的内部缺失。 这些重排导致了在分子的胞质内部分中影响两个富含半胱氨酸的结构域的框内缺失。 这些改变的克隆性质以及在多于一种肿瘤中观察到相同改变的事实表明这些突变受体蛋白在肿瘤发生中的作用。 此外，这些研究记录了由体细胞突变引起的肿瘤特异性细胞分子的存在。