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LOH11CR2A的分子克隆与特性分析,11q23区域杂合性缺失精细最小区域内的一个新基因。

Molecular cloning and characterization of LOH11CR2A, a new gene within a refined minimal region of LOH at 11q23.

作者信息

Monaco C, Negrini M, Sozzi G, Veronese M L, Vorechovsky I, Godwin A K, Croce C M

机构信息

Kimmel Cancer Institute, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

出版信息

Genomics. 1997 Dec 1;46(2):217-22. doi: 10.1006/geno.1997.5036.

Abstract

Deletions at chromosome 11q23 are frequent events in a variety of human neoplasms, including breast, lung, and ovarian carcinomas. Two common regions of loss of heterozygosity, shared between lung and breast carcinomas, have been previously identified at 11q23, suggesting that the same tumor susceptibility genes are altered in these two malignancies. One of these regions, refined in lung adenocarcinoma, is included between loci D11S1345 and D11S1328. Here, we describe the refinement of the same region in breast carcinomas and the characterization of a new gene found within this area. The gene, called LOH11CR2A, spans an area of approximately 40 kb and is transcribed at a low level in all the tissues in which it has been analyzed. The predicted amino acid primary sequence revealed no homology with other proteins that could help to elucidate a possible function for the LOH11CR2A protein. Here, we tested the hypothesis that LOH11CR2A could be a tumor suppressor gene. Analysis of human breast, lung, and ovarian carcinomas revealed the presence of several amino acid substitutions in the coding region of this gene. However, a role for these amino acid changes in the tumorigenic process could not established.

摘要

11号染色体q23区域的缺失在多种人类肿瘤中是常见事件,包括乳腺癌、肺癌和卵巢癌。先前已在11q23区域鉴定出肺癌和乳腺癌共有的两个常见杂合性缺失区域,这表明这两种恶性肿瘤中相同的肿瘤易感基因发生了改变。其中一个在肺腺癌中得到精细定位的区域位于基因座D11S1345和D11S1328之间。在此,我们描述了该区域在乳腺癌中的精细定位以及在该区域内发现的一个新基因的特征。该基因名为LOH11CR2A,跨度约40 kb,在所分析的所有组织中均低水平转录。预测的氨基酸一级序列与其他可能有助于阐明LOH11CR2A蛋白潜在功能的蛋白质没有同源性。在此,我们检验了LOH11CR2A可能是肿瘤抑制基因的假设。对人类乳腺癌、肺癌和卵巢癌的分析显示,该基因编码区存在多个氨基酸替换。然而,这些氨基酸变化在肿瘤发生过程中的作用尚未确定。

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