Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), Rockville, Maryland, USA.
Nat Genet. 2012 May 6;44(6):651-8. doi: 10.1038/ng.2270.
In an analysis of 31,717 cancer cases and 26,136 cancer-free controls from 13 genome-wide association studies, we observed large chromosomal abnormalities in a subset of clones in DNA obtained from blood or buccal samples. We observed mosaic abnormalities, either aneuploidy or copy-neutral loss of heterozygosity, of >2 Mb in size in autosomes of 517 individuals (0.89%), with abnormal cell proportions of between 7% and 95%. In cancer-free individuals, frequency increased with age, from 0.23% under 50 years to 1.91% between 75 and 79 years (P = 4.8 × 10(-8)). Mosaic abnormalities were more frequent in individuals with solid tumors (0.97% versus 0.74% in cancer-free individuals; odds ratio (OR) = 1.25; P = 0.016), with stronger association with cases who had DNA collected before diagnosis or treatment (OR = 1.45; P = 0.0005). Detectable mosaicism was also more common in individuals for whom DNA was collected at least 1 year before diagnosis with leukemia compared to cancer-free individuals (OR = 35.4; P = 3.8 × 10(-11)). These findings underscore the time-dependent nature of somatic events in the etiology of cancer and potentially other late-onset diseases.
在对来自 13 项全基因组关联研究的 31717 例癌症病例和 26136 例无癌症对照的分析中，我们在从血液或口腔样本中获得的 DNA 中观察到了一小部分克隆存在大的染色体异常。我们观察到了 517 个人（0.89%）的常染色体中存在 >2Mb 大小的嵌合体异常，包括非整倍体或拷贝数中性杂合性丢失，异常细胞比例在 7%至 95%之间。在无癌症个体中，频率随年龄增加而增加，从 50 岁以下的 0.23%增加到 75 岁至 79 岁之间的 1.91%（P=4.8×10(-8)）。嵌合体异常在实体瘤患者中更为常见（无癌症个体中为 0.74%，为 0.97%；比值比（OR）=1.25；P=0.016），与 DNA 在诊断或治疗前采集的病例的相关性更强（OR=1.45；P=0.0005）。与无癌症个体相比，在至少提前 1 年采集 DNA 的白血病患者中，可检测到的嵌合体异常也更为常见（OR=35.4；P=3.8×10(-11)）。这些发现强调了体细胞事件在癌症病因学和潜在其他迟发性疾病中的时间依赖性。
