Mutations of the TERT promoter are common in basal cell carcinoma and squamous cell carcinoma
Mutations of the TERT promoter are common in basal cell carcinoma and squamous cell carcinoma
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DOI：
10.1038/modpathol.2013.167
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发表时间：
2014-04-01
期刊：
影响因子：
7.5
通讯作者：
Rothberg, Paul G.
中科院分区：
文献类型：
--
作者：
Scott, Glynis A.;Laughlin, Todd S.;Rothberg, Paul G.
端粒酶在癌症中频繁表达，并有助于癌的发生。两个最近的出版物报告了一组复发性突变的黑色素瘤中的端粒酶逆转录酶基因（TERT）的启动子，这似乎是从紫外线（UV）辐射诱变的结果的鉴定。两个研究小组都报告说，突变增加了TERT的转录。这促使我们在另外两种与紫外线相关的皮肤癌（基底细胞癌和鳞状细胞癌）中寻找类似的突变。我们发现黑色素瘤中报告的激活性TERT启动子突变在鳞状细胞癌（50%）和基底细胞癌中也很常见，后者包括散发性肿瘤（78%）和痣样基底细胞癌综合征患者的肿瘤（68%）。在11例鲍文病（原位鳞状细胞癌）标本中仅发现1例这些突变，在15例非恶性皮肤标本和57例血液标本中均未发现。突变通常是纯合或半合的，在突变位置几乎没有或没有正常信号。这些数据表明，TERT启动子突变是皮肤癌中最常见的假定致癌突变。
Telomerase is frequently expressed in cancer and contributes to carcinogenesis. Two recent publications report the identification of a set of recurrent mutations in melanoma in the promoter of the telomerase reverse transcriptase gene (TERT) that appears to be the result of mutagenesis from ultraviolet (UV) radiation. Both groups reported that the mutations increase the transcription of TERT. This prompted our search for similar mutations in two other UV-related skin cancers, basal cell carcinoma, and squamous cell carcinoma. We found that the activating TERT promoter mutations reported in melanoma are also frequent in squamous cell carcinoma (50%) and basal cell carcinoma, the latter including both sporadic tumors (78%) and tumors from patients with nevoid basal cell carcinoma syndrome (68%). These mutations were found in only 1 of 11 Bowen's disease (squamous cell carcinoma in situ) specimens, and in none of 15 non-malignant skin specimens and 57 blood specimens. The mutations were frequently homozygous or hemizygous, with little or no normal signal at the mutated positions. These data suggest that TERT promoter mutations are the most frequent putative oncogenic mutations in cutaneous cancer.