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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Clonal expansions in ulcerative colitis identify patients with neoplasia
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Clonal expansions in ulcerative colitis identify patients with neoplasia

机译：溃疡性结肠炎的克隆性扩张可鉴别出患有肿瘤的患者

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摘要

Chronic inflammation predisposes to a variety of human cancers. Affected tissues slowly accumulate mutations, some of which affect growth regulation and drive successive waves of clonal evolution, whereas a far greater number are functionally neutral and serve only to passively mark expanding clones. Ulcerative colitis (UC) is an inflammatory bowel disease, in which up to 10% of patients eventually develop colon cancer. Here we have mapped mutations in hypermutable intergenic and intronic polyguanine tracts in patients with UC to delineate the extent of clonal expansions associated With carcinogenesis. We genotyped colon biopsies for length altering mutations at 28 different polyguanine markers. In eight patients without neoplasia, we detected only two mutations in a single individual from among 37 total biopsies. In contrast, for 11 UC patients with neoplasia elsewhere in the colon, we identified 63 mutations in 51 nondysplastic biopsies, and every patient possessed at least one mutant clone. A subset of clones were large and extended over many square centimeters of colon. Of these, some occurred as isolated populations in nondysplastic tissue, considerably distant from neoplastic lesions. Other large clones included regions of cancer, suggesting that the tumor arose within a preexisting clonal field. Our results demonstrate that neutral mutations in polyguanine tracts serve as a unique tool for identifying fields of clonal expansions, which may prove clinically useful for distinguishing a subset of UC patients who are at risk for developing cancer.
机译：慢性炎症易引发多种人类癌症。受影响的组织缓慢积累突变，其中一些影响生长调节并驱动连续的克隆进化波，而数量更多的是功能中性的，仅用于被动标记扩增的克隆。溃疡性结肠炎（UC）是一种炎症性肠病，其中多达10％的患者最终会患上结肠癌。在这里，我们绘制了UC患者超变基因间和内含子鸟嘌呤区的突变图谱，以描绘与癌变相关的克隆扩增的程度。我们对结肠活检的基因型进行了基因分型，以了解在28种不同的多鸟嘌呤标记处的长度改变突变。在8例没有肿瘤的患者中，我们在37例活检中仅检测到一个个体中的两个突变。相比之下，对于11例结肠其他部位有肿瘤的UC患者，我们在51例不典型增生的活检组织中鉴定出63个突变，并且每位患者至少拥有一个突变体克隆。克隆的一个子集很大，并延伸到结肠的许多平方厘米上。其中一些发生在非增生性组织中的孤立种群中，与肿瘤性病变相距甚远。其他大型克隆包括癌症区域，这表明该肿瘤出现在先前存在的克隆区域内。我们的结果表明，多鸟嘌呤束中的中性突变可作为鉴定克隆扩增区域的独特工具，这可能在临床上可用于区分有患癌症风险的一部分UC患者。

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    Jesse J. Salk; Stephen J. Salipante; Rosa Ana Risques; David A. Crispin; Lin Li; Mary P. Bronner; Teresa A. Brentnall; Peter S. Rabinovitch; Marshall S. Horwitz; Lawrence A. Loeb;

  • 作者单位

    Departments of Pathology, University of Washington School of Medicine, Seattle, WA 98105;

    Departments of Genome Sciences, University of Washington School of Medicine, Seattle, WA 98105;

    Departments of Pathology, University of Washington School of Medicine, Seattle, WA 98105;

    Departments of Pathology, University of Washington School of Medicine, Seattle, WA 98105;

    Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109;

    Department of Anatomic Pathology, Cleveland Clinic, Cleveland, OH 44195;

    Departments of Pathology, University of Washington School of Medicine, Seattle, WA 98105 Departments of Medicine, University of Washington School of Medicine, Seattle, WA 98105;

    Departments of Pathology, University of Washington School of Medicine, Seattle, WA 98105 Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109;

    Departments of Pathology, University of Washington School of Medicine, Seattle, WA 98105;

    Departments of Pathology, University of Washington School of Medicine, Seattle, WA 98105;

  • 收录信息 美国《科学引文索引》(SCI);美国《生物学医学文摘》(MEDLINE);美国《化学文摘》(CA);
  • 原文格式 PDF
  • 正文语种 eng
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  • 关键词

    field effect; lineage mapping; neoplastic evolution;

    机译：场效应谱系映射肿瘤演变;

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