Laterally spreading type of colorectal adenoma exhibits a unique methylation phenotype and K-ras mutations

Laterally spreading type of colorectal adenoma exhibits a unique methylation phenotype and K-ras mutations
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DOI:
10.1053/j.gastro.2006.04.027
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发表时间:
2006-08-01
期刊:
影响因子:
29.4
通讯作者:
Shiratori, Yasushi
Shiratori, Yasushi
中科院分区:
医学1区
文献类型:
--
作者:
Hiraoka, Sakiko;Kato, Jun;Shiratori, Yasushi

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背景和目的:横向扩散肿瘤(LST)的特点是沿结肠腔浅表延伸,最近通过结肠镜检查发现。然而,这些肿瘤的遗传和表观遗传特征却鲜有报道。方法:收集散发性结直肠腺瘤组织205例,其中突起型157例、颗粒型LST(G-LST)23例、扁平型LST(FLST)12例、小于1 cm扁平型13例。 CpG 岛甲基化表型 (CIMP) 通过检查 p16 的甲基化状态、肿瘤 (MINT) 1、2、12 和 31 个位点的甲基化来确定。还检查了 K-ras 密码子 12 和 13 点突变。分析宏观外观与 CIMP 状态或 K-ras 突变之间的关系。结果:在大于 1 cm 的腺瘤中,涉及 2 个或更多位点(CIMP 高)的 CpG 岛甲基化在 G-LST 中更容易观察到(14/23,61%),而不是在突出型腺瘤中(18/73,25%)(P=.002)。 G-LST中K-ras突变的发生率(18/23,78%)显着高于突出型腺瘤(18/73,25%)(P
Background & Aims: Laterally spreading tumors (LST), characterized by superficial extension along the colonic lumen, have recently been detected by colonoscopy. However, genetic and epigenetic characteristics of these tumors were scarcely reported. Methods: A total of 205 sporadic colorectal adenoma tissues (157 protruded-type, 23 granular-type LST (G-LST), 12 flat-type LST (FLST), and 13 flat-type smaller than 1 cm) were collected. CpG island methylator phenotype (CIMP) was determined by examination of methylation status at p16, methylated in tumor (MINT) 1, 2, 12, and 31 loci. K-ras codon 12 and 13 point mutations were also examined. The relationship between macroscopic appearance and CIMP status or K-ras mutations was analyzed. Results: Among adenomas larger than 1 cm, CpG island methylation involving 2 or more loci (CIMP-high) was more likely to be observed in G-LST (14/23, 61%) than in protruded-type adenomas (18/73, 25%) (P=.002). The prevalence of K-ras mutations in G-LST (18/23, 78%) was significantly higher than that in protruded-type adenomas (18/73, 25%) (P