High frequency of p16 (CDKN2/MTS-1/INK4A) inactivation in head and neck squamous cell carcinoma.
High frequency of p16 (CDKN2/MTS-1/INK4A) inactivation in head and neck squamous cell carcinoma.
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发表时间：
1996-08
期刊：
影响因子：
11.2
通讯作者：
A. Reed;J. Califano;P. Cairns;W. Westra;R. Jones;W. Koch;S. Ahrendt;Y. Eby;D. Sewell;Homaira Nawroz;J. Bartek;D. Sidransky
中科院分区：
文献类型：
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作者：
A. Reed;J. Califano;P. Cairns;W. Westra;R. Jones;W. Koch;S. Ahrendt;Y. Eby;D. Sewell;Homaira Nawroz;J. Bartek;D. Sidransky
抑癌基因 p16 (CDKN2/MTS-1/INK4A) 可通过多种遗传机制失活。我们利用新型单克隆抗体 (mAb) DCS-50 通过免疫组织化学分析了 29 例侵袭性原发性头颈鳞状细胞癌 (HNSCC) 的 p16 失活情况。原发性病变的 p16 染色与遗传分析相关，包括：(a) 对 p16 位点标记进行详细的微卫星分析，以检测纯合缺失； (b) p16的序列分析； (c) Southern 印迹分析以确定 p16 5' CpG 岛的甲基化状态。使用免疫组织化学方法，29 个头颈鳞状细胞癌肿瘤中的 24 个 (83%) 显示 p16 核染色不存在。在这 24 个肿瘤中，我们发现 16 个 (67%) 存在纯合缺失，5 个 (21%) 被甲基化，1 个在 p16 位点显示重排，1 个在外显子 1 中显示移码突变。这些数据表明：(a) p16 肿瘤抑制基因失活是头颈部鳞状细胞癌中的常见事件； (b) p16 因几个不同且排他性的事件而失活，包括纯合缺失、点突变和启动子甲基化； (c)p16基因产物表达的免疫组织化学分析是评估p16基因失活的准确且相对简单的方法。
The tumor suppressor gene p16 (CDKN2/MTS-1/INK4A) can be inactivated by multiple genetic mechanisms. We analyzed 29 invasive primary head and neck squamous cell carcinomas (HNSCC) for p16 inactivation with immunohistochemistry utilizing a new monoclonal antibody (mAb), DCS-50. p16 staining of the primary lesions was correlated with genetic analysis including: (a) detailed microsatellite analysis of markers at the p16 locus to detect homozygous deletion; (b) sequence analysis of p16; and (c) Southern blot analysis to determine the methylation status of the 5' CpG island of p16. Twenty-four of 29 (83%) head and neck squamous cell carcinoma tumors displayed an absence of p16 nuclear staining using immunohistochemistry. Of these 24 tumors, we found that 16 (67%) harbored homozygous deletions, 5 (21%) were methylated, 1 displayed a rearrangement at the p16 locus, and 1 displayed a frameshift mutation in exon 1. These data suggest that: (a) inactivation of the p16 tumor suppressor gene is a frequent event in squamous cell carcinomas of the head and neck; (b) p16 is inactivated by several distinct and exclusive events including homozygous deletion, point mutation, and promoter methylation; and (c) immunohistochemical analysis for expression of the p16 gene product is an accurate and relatively simple method for evaluating p16 gene inactivation.