1] Department of Dermatology, University of Rochester School of Medicine, Rochester, NY, USA [2] Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine, Rochester, NY, USA.
Department of Pathology and Laboratory Medicine, University of Rochester School of Medicine, Rochester, NY, USA.
Mod Pathol. 2014 Apr;27(4):516-23. doi: 10.1038/modpathol.2013.167. Epub 2013 Sep 13.
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.
端粒酶在癌症中经常表达，有助于癌症的发生。最近的两项研究报告了在端粒酶逆转录酶基因（TERT）启动子中发现了一组黑色素瘤的复发性突变，这些突变似乎是紫外线（UV）辐射引起的突变的结果。这两个研究小组都报告称，这些突变增加了 TERT 的转录。这促使我们在另外两种与紫外线有关的皮肤癌——基底细胞癌和鳞状细胞癌中寻找类似的突变。我们发现，黑色素瘤中报道的激活 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%）和神经嵴基底细胞痣综合征患者的肿瘤（68%）。这些突变仅在 11 个 Bowen 病（原位鳞状细胞癌）标本中的 1 个中发现，在 15 个非恶性皮肤标本和 57 个血液标本中均未发现。这些突变通常是纯合子或半合子的，在突变部位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潜在致癌突变。
