The landscape of driver mutations in cutaneous squamous cell carcinoma.
The landscape of driver mutations in cutaneous squamous cell carcinoma.
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DOI：
10.1038/s41525-021-00226-4
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发表时间：
2021-07-16
影响因子：
5.3
通讯作者：
Shain AH
中科院分区：
文献类型：
--
作者：
Chang D;Shain AH
皮肤鳞状细胞癌是一种起源于皮肤角质形成细胞的皮肤癌。它是第二种最常见的癌症，在美国每年估计有8000人死亡。与具有相似发病率和死亡人数的其他癌症亚型相比，我们对驱动皮肤鳞状细胞癌的体细胞突变的理解是有限的。主要的挑战是这些肿瘤具有高突变负担，主要是紫外线辐射诱导的阳光DNA损伤的结果，使得难以区分驱动突变和乘客突变。我们通过对来自10项不同研究的105种肿瘤的公开测序数据进行荟萃分析，克服了这一挑战。此外，我们消除了具有问题的肿瘤，例如肿瘤细胞含量低，并且从通过质量控制的肿瘤中，我们利用多种策略来揭示选择中的基因。我们总共提名了30个癌症基因。在更多的新基因中，突变经常影响EP 300，PBRM 1，USP 28和CHUK。总的来说，NOTCH和p53途径中的突变是普遍存在的，并且在较小程度上，突变影响Hippo途径中的基因、Ras/MAPK/PI 3 K途径中的基因、对细胞周期检查点控制至关重要的基因以及编码染色质重塑因子的基因。总之，我们的研究提供了皮肤鳞状细胞癌中驱动基因的目录，提供了治疗干预的要点和对皮肤鳞状细胞癌生物学的见解。
Cutaneous squamous cell carcinoma is a form of skin cancer originating from keratinocytes in the skin. It is the second most common type of cancer and is responsible for an estimated 8000 deaths per year in the United States. Compared to other cancer subtypes with similar incidences and death tolls, our understanding of the somatic mutations driving cutaneous squamous cell carcinoma is limited. The main challenge is that these tumors have high mutation burdens, primarily a consequence of UV-radiation-induced DNA damage from sunlight, making it difficult to distinguish driver mutations from passenger mutations. We overcame this challenge by performing a meta-analysis of publicly available sequencing data covering 105 tumors from 10 different studies. Moreover, we eliminated tumors with issues, such as low neoplastic cell content, and from the tumors that passed quality control, we utilized multiple strategies to reveal genes under selection. In total, we nominated 30 cancer genes. Among the more novel genes, mutations frequently affected EP300, PBRM1, USP28, and CHUK. Collectively, mutations in the NOTCH and p53 pathways were ubiquitous, and to a lesser extent, mutations affected genes in the Hippo pathway, genes in the Ras/MAPK/PI3K pathway, genes critical for cell-cycle checkpoint control, and genes encoding chromatin remodeling factors. Taken together, our study provides a catalog of driver genes in cutaneous squamous cell carcinoma, offering points of therapeutic intervention and insights into the biology of cutaneous squamous cell carcinoma.
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DOI：
10.1158/1541-7786.mcr-17-0260
发表时间：
2018-01
期刊：
Molecular cancer research : MCR
影响因子：
--
作者：
Duex JE;Swain KE;Dancik GM;Paucek RD;Owens C;Churchill MEA;Theodorescu D
通讯作者：
Theodorescu D
影响因子：
13.8
作者：
Karia, Pritesh S.;Han, Jiali;Schmults, Chrysalyne D.
通讯作者：
Schmults, Chrysalyne D.
影响因子：
8.8
作者：
Harwood, C. A.;Attard, N. R.;Donovan, P. O';Chambers, P.;Perrett, C. M.;Proby, C. M.;McGregor, J. M.;Karran, P.
通讯作者：
Karran, P.
影响因子：
158.5
作者：
Lahtela, Jenni;Nousiainen, Heidi O.;Kestila, Marjo
通讯作者：
Kestila, Marjo
影响因子：
28.2
作者：
Chang MT;Bhattarai TS;Schram AM;Bielski CM;Donoghue MTA;Jonsson P;Chakravarty D;Phillips S;Kandoth C;Penson A;Gorelick A;Shamu T;Patel S;Harris C;Gao J;Sumer SO;Kundra R;Razavi P;Li BT;Reales DN;Socci ND;Jayakumaran G;Zehir A;Benayed R;Arcila ME;Chandarlapaty S;Ladanyi M;Schultz N;Baselga J;Berger MF;Rosen N;Solit DB;Hyman DM;Taylor BS
通讯作者：
Taylor BS