Understanding the Molecular Genetics of Basal Cell Carcinoma.
Understanding the Molecular Genetics of Basal Cell Carcinoma.
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DOI：
10.3390/ijms18112485
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发表时间：
2017-11-22
影响因子：
5.6
通讯作者：
Fargnoli MC
中科院分区：
文献类型：
--
作者：
Pellegrini C;Maturo MG;Di Nardo L;Ciciarelli V;Gutiérrez García-Rodrigo C;Fargnoli MC
基底细胞癌（BCC）是最常见的人类癌症，并代表了日益增长的公共卫生保健问题。几种肿瘤抑制基因和原癌基因与BCC发病机制有关，包括Hedgehog途径的关键组分、PTCH 1和SMO、TP 53肿瘤抑制基因和RAS原癌基因家族的成员。Hedgehog通路的异常激活代表了基底细胞癌发病机制中的分子驱动因素，大多数BCC携带体细胞点突变，主要是紫外线（UV）诱导的和/或PTCH 1基因杂合性拷贝丢失。测序技术的最新进展允许基因组规模的方法来发现突变，识别可能参与BCC致癌的新基因和途径。突变和功能分析表明PTPN 14和LATS 1，Hippo-YAP通路的效应子，以及MYCN是新的BCC相关基因。此外，新出现的报告确定了在TERT和DPH 3-OXNAD 1基因的调控启动子序列内频繁的非编码突变。因此，很明显，一个比以前假设的更复杂的癌症相关基因的遗传网络参与了BCC的致癌作用，对新的分子靶向治疗的发展具有潜在的影响。本文综述了基底细胞癌发病机制的分子遗传学方面的知识和新的假说。
Basal cell carcinoma (BCC) is the most common human cancer and represents a growing public health care problem. Several tumor suppressor genes and proto-oncogenes have been implicated in BCC pathogenesis, including the key components of the Hedgehog pathway, PTCH1 and SMO, the TP53 tumor suppressor, and members of the RAS proto-oncogene family. Aberrant activation of the Hedgehog pathway represents the molecular driver in basal cell carcinoma pathogenesis, with the majority of BCCs carrying somatic point mutations, mainly ultraviolet (UV)-induced, and/or copy-loss of heterozygosis in the PTCH1 gene. Recent advances in sequencing technology allowed genome-scale approaches to mutation discovery, identifying new genes and pathways potentially involved in BCC carcinogenesis. Mutational and functional analysis suggested PTPN14 and LATS1, both effectors of the Hippo–YAP pathway, and MYCN as new BCC-associated genes. In addition, emerging reports identified frequent non-coding mutations within the regulatory promoter sequences of the TERT and DPH3-OXNAD1 genes. Thus, it is clear that a more complex genetic network of cancer-associated genes than previously hypothesized is involved in BCC carcinogenesis, with a potential impact on the development of new molecular targeted therapies. This article reviews established knowledge and new hypotheses regarding the molecular genetics of BCC pathogenesis.
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影响因子：
5.4
作者：
Aubrey, Brandon J.;Strasser, Andreas;Kelly, Gemma L.
通讯作者：
Kelly, Gemma L.
影响因子：
--
作者：
Cucchi D;Occhione MA;Gulino A;De Smaele E
通讯作者：
De Smaele E
DOI：
10.1038/nrc2503
发表时间：
2008-10
期刊：
Nature reviews. Cancer
影响因子：
--
作者：
通讯作者：
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影响因子：
4
作者：
Deng, Wentao;Vanderbilt, Daniel B.;Ruppert, J. Michael
通讯作者：
Ruppert, J. Michael
转移性基底细胞和皮肤鳞状细胞癌对抗PD1单克隆抗体regn2810的反应。
影响因子：
10.9
作者：
Falchook GS;Leidner R;Stankevich E;Piening B;Bifulco C;Lowy I;Fury MG
通讯作者：
Fury MG