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首页> 外文期刊>Cancer prevention research. >Understanding Intratumoral Heterogeneity: Lessons from the Analysis of At-Risk Tissue and Premalignant Lesions in the Colon
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Understanding Intratumoral Heterogeneity: Lessons from the Analysis of At-Risk Tissue and Premalignant Lesions in the Colon

机译：理解肿瘤内异质性：结肠癌组织和癌前病变分析的经验教训

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Advances in DNA sequencing have created new opportunities to better understand the biology of cancers. Attention is currently focused on precision medicine: does a cancer carry a mutation that is targetable with already available drugs? But, the timing at which multiple, targetable mutations arise during the adenoma to carcinoma sequence remains unresolved. Borras and colleagues identified mutations and allelic imbalance in at-risk mucosa and early polyps in the human colon. Their analyses indicate that mutations in key genes can arise quite early during tumorigenesis and that polyps are often multiclonal with at least two clones. These results are consistent with the "Big Bang" model of tumorigenesis, which postulates that intratumoral heterogeneity is a consequence of a mutational burst in the first few cell divisions following initiation that drives divergence from a single founder with unique but related clones coevolving. Emerging questions center around the ancestry of the tumor and impact of early intratumoral heterogeneity on tumor establishment, growth, progression, and most importantly, response to therapeutic intervention. Additional sequencing studies in which samples, especially at-risk tissue and premalignant neoplasms, are analyzed from animal models and humans will further our understanding of tumorigenesis and lead to more effective strategies for prevention and treatment. (C) 2016 AACR.
机译：DNA测序的进步为更好地了解癌症生物学创造了新的机会。当前，注意力集中在精密医学上：癌症是否携带一种可以利用现有药物靶向的突变？但是，在腺瘤至癌序列期间出现多个可靶向突变的时机仍未解决。 Borras及其同事在人类结肠中的高风险粘膜和早期息肉中发现了突变和等位基因失衡。他们的分析表明，关键基因的突变可在肿瘤发生期间很早就出现，息肉通常是多克隆的，至少有两个克隆。这些结果与肿瘤发生的“大爆炸”模型相吻合，该模型假定肿瘤内异质性是启动后最初几个细胞分裂中突变爆发的结果，该突变导致单个创始人与独特但相关克隆共同进化的分化。新兴问题围绕着肿瘤的起源以及早期肿瘤内异质性对肿瘤形成，生长，进展以及最重要的是对治疗干预的反应的影响。从动物模型和人类中分析样品，尤其是处于危险中的组织和恶变前肿瘤的其他测序研究，将进一步加深我们对肿瘤发生的理解，并导致更有效的预防和治疗策略。 （C）2016 AACR。

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