Robles Ana I, Jen Jin, Harris Curtis C
Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Department of Laboratory Medicine and Pathology, Division of Experimental Pathology, and Department of Medicine, Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota 55905.
Cold Spring Harb Perspect Med. 2016 Sep 1;6(9):a026294. doi: 10.1101/cshperspect.a026294.
High-throughput sequencing of cancer genomes is increasingly becoming an essential tool of clinical oncology that facilitates target identification and targeted therapy within the context of precision medicine. The cumulative profiles of somatic mutations in cancer yielded by comprehensive molecular studies also constitute a fingerprint of historical exposures to exogenous and endogenous mutagens, providing insight into cancer evolution and etiology. Mutational signatures that were first established by inspection of the TP53 gene somatic landscape have now been confirmed and expanded by comprehensive sequencing studies. Further, the degree of granularity achieved by deep sequencing allows detection of low-abundance mutations with clinical relevance. In tumors, they represent the emergence of small aggressive clones; in normal tissues, they signal a mutagenic exposure related to cancer risk; and, in blood, they may soon become effective surveillance tools for diagnostic purposes and for monitoring of cancer prognosis and recurrence.
癌症基因组的高通量测序日益成为临床肿瘤学的一项重要工具,有助于在精准医疗背景下进行靶点识别和靶向治疗。全面分子研究产生的癌症体细胞突变累积图谱也构成了对外源性和内源性诱变剂历史暴露的指纹,为癌症进化和病因学提供了见解。最初通过检查TP53基因体细胞图谱建立的突变特征现已通过全面测序研究得到证实和扩展。此外,深度测序实现的精细程度允许检测具有临床相关性的低丰度突变。在肿瘤中,它们代表小侵袭性克隆的出现;在正常组织中,它们表明与癌症风险相关的诱变暴露;而在血液中,它们可能很快成为用于诊断目的以及监测癌症预后和复发的有效监测工具。