摘要：美韩等国科学家7月1日发表研究报告称，某个基因的突变可能是正常细胞转变成癌细胞的最早征兆。这一发现将有助于早期发现和及时治疗癌症。
癌细胞由正常细胞“异化”而来，在此过程中发生一系列基因突变。有些突变远在正常细胞癌化之前就已发生，这些最早突变的基因，可能成为癌症早期诊断的“风向标”。研究人员必须根据癌细胞现有基因序列确定基因的突变时间，这一工作相当于基因研究中的“考古学”。
美国加州大学旧金山分校和伯克利分校、俄勒冈卫生科学大学及韩国三星先进技术研究所等机构的研究人员在最新一期《癌症发现》期刊上报告说，他们对两种原发性癌细胞的TP53基因分析表明，在多数情况下，这个基因的突变是在细胞癌化之前最早发生的，而不是原先所认为的那样在癌化后发生。
研究人员分析了常见皮肤癌——鳞状细胞瘤和常见卵巢癌——浆液性卵巢腺瘤中癌细胞的基因突变过程后发现，TP53基因的序列早在细胞癌化之前就已异常复制。TP53是已知的致癌基因，与这两种癌症密切相关。
生物探索推荐英文论文摘要：
Temporal Dissection of Tumorigenesis in Primary Cancers
Abstract：
Timely intervention for cancer requires knowledge of its earliest genetic aberrations. Sequencing of tumors and their metastases reveals numerous abnormalities occurring late in progression. A means to temporally order aberrations in a single cancer, rather than inferring them from serially acquired samples, would define changes preceding even clinically evident disease. We integrate DNA sequence and copy number information to reconstruct the order of abnormalities as individual tumors evolve for 2 separate cancer types. We detect vast, unreported expansion of simple mutations sharply demarcated by recombinative loss of the second copy of TP53 in cutaneous squamous cell carcinomas (cSCC) and serous ovarian adenocarcinomas, in the former surpassing 50 mutations per megabase. In cSCCs, we also report diverse secondary mutations in known and novel oncogenic pathways, illustrating how such expanded mutagenesis directly promotes malignant progression. These results reframe paradigms in which TP53 mutation is required later, to bypass senescence induced by driver oncogenes.
Significance: Our approach reveals sequential ordering of oncogenic events in individual cancers, based on chromosomal rearrangements. Identifying the earliest abnormalities in cancer represents a critical step in timely diagnosis and deployment of targeted therapeutics. Cancer Discovery; 1(2); OF1–OF7. © 2011 AACR.
