Shibata D, Navidi W, Salovaara R, Li Z H, Aaltonen L A
Department of Pathology, University of Southern California School of Medicine, Los Angeles 90033, USA.
Nat Med. 1996 Jun;2(6):676-81. doi: 10.1038/nm0696-676.
Microsatellite (MS) mutations can potentially unravel the past of mutator phenotype tumors, with greater genetic diversity expected in older regions. Rapid clonal expansions of xenografts were characterized by relatively homogenous MS alleles, whereas greater diversity was observed in a colorectal cancer with the greatest variation in its adjacent adenoma. A subcutaneous lung cancer metastasis demonstrated diversity consistent with its one-month clinical duration and evidence of active mitosis during dormancy. The genetic legacy inherent to multistep tumorigenesis provides direct estimates of tumor ages, with up to thousands of cell divisions and high death rates necessary to yield the observed diversities. MS molecular tumor clocks have the unique potential to systematically reconstruct the early and occult evolution of individual human mutator phenotype tumors.
微卫星（MS）突变可能揭示具有突变体表型肿瘤的过去，预计在较老区域具有更大的遗传多样性。异种移植的快速克隆扩增以相对同质的MS等位基因为特征，而在相邻腺瘤中变化最大的结直肠癌中观察到更大的多样性。皮下肺癌转移灶表现出与其一个月临床病程一致的多样性以及休眠期间活跃有丝分裂的证据。多步骤肿瘤发生所固有的遗传遗产提供了肿瘤年龄的直接估计，产生观察到的多样性需要多达数千次细胞分裂和高死亡率。MS分子肿瘤时钟具有系统重建个体人类突变体表型肿瘤早期和隐匿性演变的独特潜力。
