Genome-wide DNA copy number alterations in head and neck squamous cell carcinomas with or without oncogene-expressing human papillomavirus
Genome-wide DNA copy number alterations in head and neck squamous cell carcinomas with or without oncogene-expressing human papillomavirus
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DOI：
10.1038/sj.onc.1209275
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发表时间：
2006-04-01
期刊：
影响因子：
8
通讯作者：
Brakenhoff, RH
中科院分区：
文献类型：
--
作者：
Smeets, SJ;Braakhuis, BJM;Brakenhoff, RH
表达癌基因的人乳头瘤病毒16型（HPV 16）见于头颈部鳞状细胞癌（HNSCC）的一个亚群。HPV 16通过用病毒癌蛋白E6和E7使p53和pRb失活来驱动癌发生，其次是TP 53的低水平突变和3 p、9 p和17 p的等位基因丢失，这些遗传变化经常在非病毒病因的HNSCC中发现。我们假设HNSCC存在两种途径：一种由HPV 16决定，另一种由环境致癌物决定。敬德。在这两个途径的关键遗传事件，我们现在提出了一个详细的基因组分析HNSCC与HPV 16的参与和不参与，采用高分辨率微阵列比较基因组杂交。在HPV阴性肿瘤中有四个区域显示出HPV阳性肿瘤中不存在的改变：3p11.2-26.3、5q11.2-35.2和9p21.1-24的丢失，以及11q12.1-13.4的增益/扩增。此外，HPV 16阴性肿瘤显示18q12.1-23缺失，与HPV 16阳性肿瘤的增加相反。两组中有7个区域发生了高频改变（> 33%）：3q22.2-qter、5p15.2-pter、8p11.2-qter、9 q22 -34.1和20 p-20 q增加，11q14.1-qter和13 q11 -33丢失。这些数据表明，HNSCC由环境致癌物引起的特征在于与HPV 16诱导的HNSCC中观察到的遗传改变不同的遗传改变，并且最有可能发生在致癌作用的早期。许多遗传变化在两个肿瘤组中共享，并且可以被认为在HNSCC进展的后期阶段至关重要。
Oncogene-expressing human papillomavirus type 16 (HPV16) is found in a subset of head and neck squamous cell carcinomas (HNSCC). HPV16 drives carcinogenesis by inactivating p53 and pRb with the viral oncoproteins E6 and E7, paralleled by a low level of mutations in TP53 and allelic loss at 3p, 9p, and 17p, genetic changes frequently found in HNSCCs of nonviral etiology. We hypothesize that two pathways to HNSCC exist: one determined by HPV16 and the other by environmental carcinogens. To de. ne the critical genetic events in these two pathways, we now present a detailed genome analysis of HNSCC with and without HPV16 involvement by employing high-resolution microarray comparative genomic hybridization. Four regions showed alterations in HPV-negative tumors that were absent in HPV-positive tumors: losses at 3p11.2-26.3, 5q11.2-35.2, and 9p21.1-24, and gains/amplifications at 11q12.1-13.4. Also, HPV16-negative tumors demonstrated loss at 18q12.1-23, in contrast to gain in HPV16-positive tumors. Seven regions were altered at high frequency (> 33%) in both groups: gains at 3q22.2-qter, 5p15.2-pter, 8p11.2-qter, 9q22-34.1, and 20p-20q, and losses at 11q14.1-qter and 13q11-33. These data show that HNSCC arising-by environmental carcinogens are characterized by genetic alterations that differ from those observed in HPV16-induced HNSCC, and most likely occur early in carcinogenesis. A number of genetic changes are shared in both tumor groups and can be considered crucial in the later stages of HNSCC progression.