Higher frequency of alterations in the p16/CDKN2 gene in squamous cell carcinoma cell lines than in primary tumors of the head and neck.
Higher frequency of alterations in the p16/CDKN2 gene in squamous cell carcinoma cell lines than in primary tumors of the head and neck.
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发表时间：
1994-10
期刊：
影响因子：
11.2
通讯作者：
S. Y. Zhang;Andres J Klein-Szanto;E. Sauter;M. Shafarenko;S. Mitsunaga;T. Nobori;D. Carson;J. Ridge;T. Goodrow
中科院分区：
文献类型：
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作者：
S. Y. Zhang;Andres J Klein-Szanto;E. Sauter;M. Shafarenko;S. Mitsunaga;T. Nobori;D. Carson;J. Ridge;T. Goodrow
对68例原发性头颈部鳞状细胞癌和9例头颈部鳞状细胞癌细胞系进行p16/CDKN2基因突变和纯合缺失检测。在3个细胞系中发现p16/CDKN2基因纯合缺失，在另一个细胞系中发现突变。相比之下，原发肿瘤中没有一例出现纯合缺失，68例肿瘤中有11例出现错义或无义碱基改变。7个肿瘤包含体细胞突变。五个肿瘤，包括一个也有体细胞突变的肿瘤，在密码子140上可能存在多态性，导致氨基酸从Ala变为Thr。其中三个在密码子98处也有明显的多态性，这不会导致氨基酸的变化。检测到的突变和缺失的频率在细胞系（44%）和原发肿瘤（10%）之间存在显著差异，这表明尽管p16/CDKN2可能在某些头颈部鳞状细胞癌的肿瘤发生中发挥作用，但由于适应细胞培养，p16/CDKN2的失活可能在细胞系中更频繁地发生。
Sixty-eight primary head and neck squamous cell carcinomas and nine head and neck squamous cell carcinoma cell lines were examined for mutations and homozygous deletions of the p16/CDKN2 gene. Homozygous deletions of the p16/CDKN2 gene were found in three lines, and a mutation was detected in another cell line. In contrast, none of the primary tumors showed homozygous deletions and 11 of 68 tumors had missense or nonsense base changes. Seven tumors contained somatic mutations. Five tumors, including one that also had a somatic mutation, had a probable polymorphism at codon 140 leading to an amino acid change from Ala to Thr. Three of these also contained an apparent polymorphism at codon 98, which did not lead to an amino acid change. The frequency of mutations and deletions detected differs markedly between cell lines (44%) and primary tumors (10%) suggesting that while p16/CDKN2 may play a role in tumorigenesis in some head and neck squamous cell carcinomas, inactivation of p16/CDKN2 probably occurs more frequently in cell lines as a result of adaptation to cell culture.