Schuuring E
Department of Pathology, University of Leiden, The Netherlands.
Gene. 1995 Jun 14;159(1):83-96. doi: 10.1016/0378-1119(94)00562-7.
Amplification of oncogenes has been observed frequently in various human malignancies and might be of clinical relevance. In the last decade, the exploration of oncogene activation due to DNA amplification in cancer research has mainly focussed on three aspects: (i) the assessment of oncogene amplification as a prognostic marker for survival of cancer patients, (ii) the development of reliable methods for detection of tumors which harbor DNA amplification of oncogenes and (iii) the identification of the gene or genes responsible for the biological (prognostic) significance in tumors with DNA amplification and the characterization of these candidate proto-oncogenes that might help to elucidate their normal function and the role in tumor development. In this review, these three aspects will be highlighted with regard to DNA amplification of the chromosome 11q13 region. Chromosome 11q13 amplification has been found frequently in certain human malignancies; in cancer of the breast and of the head and neck region, amplification of this region is observed in 13 and 29% of tumors, respectively. The 11q13 amplification has been reported to be of clinical relevance in these cancers, since patients with this amplification show a poor clinical course of disease. The amplified 11q13 region is estimated to be 3-5 Mb in size and to harbor many (putative) genes. Recently, two candidate genes, CCND1 and EMS1, were identified which were both over-expressed in all carcinomas with an 11q13 amplification. Therefore, the activation of these genes might confer the selective advantage to these tumors. In addition, the characterization of these two novel genes sustained their potential role in carcinomas with 11q13 amplification.
在各种人类恶性肿瘤中,癌基因扩增现象屡见不鲜,且可能具有临床意义。在过去十年中,癌症研究中对因DNA扩增导致的癌基因激活的探索主要集中在三个方面:(i)评估癌基因扩增作为癌症患者生存预后标志物;(ii)开发检测存在癌基因DNA扩增肿瘤的可靠方法;(iii)鉴定在DNA扩增肿瘤中具有生物学(预后)意义的一个或多个基因,并对这些候选原癌基因进行表征,这可能有助于阐明其正常功能以及在肿瘤发生发展中的作用。在本综述中,将围绕11号染色体q13区域的DNA扩增重点阐述这三个方面。在某些人类恶性肿瘤中经常发现11号染色体q13扩增;在乳腺癌和头颈部癌中,分别有13%和29%的肿瘤观察到该区域的扩增。据报道,11q13扩增在这些癌症中具有临床相关性,因为具有这种扩增的患者疾病临床进程较差。扩增的11q13区域估计大小为3 - 5 Mb,包含许多(假定的)基因。最近,鉴定出两个候选基因CCND1和EMS1,在所有11q13扩增的癌组织中均过度表达。因此,这些基因的激活可能赋予这些肿瘤选择性优势。此外,对这两个新基因的表征证实了它们在11q13扩增癌中的潜在作用。