Frequent mutation of p16 in squamous cell carcinoma of the head and neck
Frequent mutation of p16 in squamous cell carcinoma of the head and neck
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DOI：
10.1097/00005537-199806000-00024
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发表时间：
1998-06-01
期刊：
影响因子：
2.6
通讯作者：
Weghorst, CM
中科院分区：
文献类型：
--
作者：
Lang, JC;Tobin, EJ;Weghorst, CM
从22例头颈部不同部位的鳞状细胞癌(SCCs)和可用的配对正常组织中分离出RNA。采用半定量逆转录聚合酶链式反应(RT-PCR)检测组织标本中抑癌基因p16的RNA表达。从肿瘤样本产生的p16特异性PCR扩增产物通过直接DNA测序进行进一步分析，以确定是否有任何肿瘤样本含有p16突变。结果显示，在22个肿瘤样本中，有10个(45%)存在突变。突变包括两个相同的点突变、两个小的缺失(1个碱基和2个碱基)、一个单核苷酸插入、四个较大的缺失和一个插入/缺失。通过对正常匹配组织产生的PCR产物的分析，没有发现p16基因突变，这表明p16基因突变是由体细胞突变产生的，而不是起源于生殖系。免疫组织化学方法检测22例视网膜母细胞瘤(Rb)抑癌基因产物的核表达。结果显示，仅有1例标本未见RE核表达，提示RE突变在头颈部鳞状细胞癌(SCCHN)的发生发展中是一种罕见的事件。
RNA was isolated from 22 squamous cell carcinomas (SCCs) obtained from diverse sites within the head and neck and from matched normal tissue where available. Tissue samples were then screened for expression of RNA from tumor suppressor gene p16 by utilizing semiquantitative reverse transcriptase polymerase chain reaction (RT-PCR) analysis. p16-Specific PCR amplification products generated from tumor samples were subject to further analysis by direct DNA sequencing to determine if any tumor sample harbored a p16 mutation. The results show the presence of mutations in 10 of 22 (45%) of the tumor samples. Mutations comprise two identical point mutations, two small deletions (1 bp and 2 bp), one single-nucleotide insertion, four larger deletions, and an insertion/deletion. No mutations in p16 have been identified by analysis of PCR products generated from normal matched tissue, suggesting that p16 alterations are generated by somatic mutation and are not germline in origin. All 22 samples were analyzed additionally by immunohistochemistry for nuclear expression of the retinoblastoma (RB) tumor suppressor gene product. Results show lack of RE nuclear expression in only one sample, suggesting that mutation of RE is an infrequent event in the development of SCC of the head and neck (SCCHN).