Differential mutation frequencies in metastatic cutaneous squamous cell carcinomas versus primary tumors.
Differential mutation frequencies in metastatic cutaneous squamous cell carcinomas versus primary tumors.
复制标题
DOI：
10.1002/cncr.30459
复制
发表时间：
2017-04-01
期刊：
影响因子：
6.2
通讯作者：
Toland AE
中科院分区：
文献类型：
--
作者：
Yilmaz AS;Ozer HG;Gillespie JL;Allain DC;Bernhardt MN;Furlan KC;Castro LT;Peters SB;Nagarajan P;Kang SY;Iwenofu OH;Olencki T;Teknos TN;Toland AE
外显子组和靶向测序研究已经确定了各种肿瘤类型的潜在驱动突变。皮肤鳞状细胞癌（cSCC）是最高度突变的癌症之一，但通常与低转移率和高存活率相关。然而，转移性cSCC是一个重大的健康威胁;每年多达8800人死于这种疾病。由于很难预测哪些cSCC更有可能转移，并且由于没有专门针对转移性cSCC的靶向治疗，我们对18例转移性和10例原发性cSCC进行了外显子组和/或靶向测序，以鉴定在转移性肿瘤中更常见的突变，并且可能靶向治疗获益。我们将我们的结果与另外223例原发性肿瘤和68例转移性cSCC的已发表测序结果进行了比较。我们鉴定了在转移性cSCC中相对于原发性肿瘤显示更高突变频率的基因，包括染色质重塑基因KMT 2D和经典皮肤肿瘤抑制基因TP 53，其在54%的原发性肿瘤中突变，而在85%的转移性肿瘤中突变（p <0.0001）。这些研究揭示了转移性cSCC中重要的潜在途径，拓宽了我们对促进侵袭性肿瘤行为的生物学的理解，并可能导致新的治疗策略。
Exome and targeted sequencing studies have identified potential driver mutations for a variety of tumor types. Cutaneous squamous cell carcinoma (cSCC) is one of the most highly mutated cancers but is typically associated with low rates of metastasis and high survival rates. Nevertheless, metastatic cSCC is a significant health threat; up to 8800 individuals die yearly from this disease. As it is difficult to predict which cSCCs are more likely to metastasize, and because there are no targeted therapies specifically designated for metastatic cSCC, we performed exome and/or targeted sequencing of 18 metastatic and 10 primary cSCCs to identify mutations that were more frequent in metastatic tumors and might be targeted for therapeutic benefit. We compared our results to published sequencing results of an additional 223 primary tumors and 68 metastatic cSCCs. We identified genes showing higher mutation frequencies in metastatic cSCC relative to primary tumors including the chromatin remodeling gene KMT2D and the classic skin tumor suppressor TP53 which was mutated in 54% of primary tumors relative to 85% of metastatic tumors (p <0.0001). These studies uncover potential pathways important in metastatic cSCC that broaden our understanding of the biology contributing to aggressive tumor behavior and may lead to new therapeutic strategies.