Array-based comparative genomic hybridization in ulcerative colitis neoplasia: single non-dysplastic biopsies distinguish progressors from non-progressors
Array-based comparative genomic hybridization in ulcerative colitis neoplasia: single non-dysplastic biopsies distinguish progressors from non-progressors
复制标题
DOI：
10.1038/modpathol.2010.161
复制
发表时间：
2010-12-01
期刊：
影响因子：
7.5
通讯作者：
Brentnall, Teresa A.
中科院分区：
文献类型：
--
作者：
Bronner, Mary P.;Skacel, Marek;Brentnall, Teresa A.
大约10%的溃疡性结肠炎患者会发生结直肠肿瘤。目前，对这一亚群的识别明显有限，需要对整个溃疡性结肠炎人群进行终身结肠镜监测。需要更好的风险标记，以便将监测重点放在最有可能受益的患者身上。使用基于阵列的比较基因组杂交技术，我们分析了来自三组患者的单一非发育不良活检：溃疡性结肠炎进展者（n=9），与分析部位的平均距离为18cm，患有癌症或高度发育不良；溃疡性结肠炎未进展者（n=8）在长期监测期间无发育不良；非溃疡性结肠炎正常对照组（n=2）。从基质中纯化的新鲜结肠上皮细胞的基因组DNA与287（低密度）和4342（高密度）特征细菌人工染色体阵列杂交。计算单个染色体靶点和整个基因组的样品-参考荧光比。低密度阵列在9名溃疡性结肠炎进展患者中有3名（33%）产生了明显的基因组增益和损失，但在10名对照患者中没有。在高密度阵列上分析相同的DNA样本，结合使用全局和个体高方差评估，将所有9名进展者与所有10名对照者区分开来。这些数据证实，溃疡性结肠炎进展者的基因组改变是普遍存在的，甚至涉及远离肿瘤的单一非发育不良活检。因此，在大多数溃疡性结肠炎患者中，它们有望消除广泛活检取样的全结肠镜监测。现代病理学（2010）23,1624-1633；doi: 10.1038 / modpathol.2010.161;2010年8月27日在线发布
Approximately 10% of ulcerative colitis patients develop colorectal neoplasia. At present, identification of this subset is markedly limited and necessitates lifelong colonoscopic surveillance for the entire ulcerative colitis population. Better risk markers are needed to focus surveillance onto the patients who are most likely to benefit. Using array-based comparative genomic hybridization, we analyzed single, non-dysplastic biopsies from three patient groups: ulcerative colitis progressors (n=9) with cancer or high-grade dysplasia at a mean distance of 18cm from the analyzed site; ulcerative colitis non-progressors (n=8) without dysplasia during long-term surveillance; and non-ulcerative colitis normal controls (n=2). Genomic DNA from fresh colonic epithelium purified from stroma was hybridized to 287 (low-density) and 4342 (higher-density) feature bacterial artificial chromosome arrays. Sample-to-reference fluorescence ratios were calculated for individual chromosomal targets and globally across the genome. The low-density arrays yielded pronounced genomic gains and losses in 3 of 9 (33%) ulcerative colitis progressors but in none of the 10 control patients. Identical DNA samples analyzed on the higher-density arrays, using a combination of global and individual high variance assessments, distinguished all nine progressors from all 10 controls. These data confirm that genomic alterations in ulcerative colitis progressors are widespread, even involving single non-dysplastic biopsies that are far distant from neoplasia. They therefore show promise toward eliminating full colonoscopic surveillance with extensive biopsy sampling in the majority of ulcerative colitis patients. Modern Pathology (2010) 23, 1624-1633; doi:10.1038/modpathol.2010.161; published online 27 August 2010