Hiraoka Sakiko, Kato Jun, Tatsukawa Masashi, Harada Keita, Fujita Hideyuki, Morikawa Tamiya, Shiraha Hidenori, Shiratori Yasushi
Department of Gastroenterology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.
Gastroenterology. 2006 Aug;131(2):379-89. doi: 10.1053/j.gastro.2006.04.027.
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.
A total of 205 sporadic colorectal adenoma tissues (157 protruded-type, 23 granular-type LST (G-LST), 12 flat-type LST (F-LST), 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.
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 < .0001). Moreover, the prevalence of CIMP-high and K-ras mutations in G-LST located in the proximal colon was much higher (11/13, 85%; and 12/13, 92%, respectively). In contrast, F-LST exhibited low prevalence of CIMP-high (1/12, 8%) and K-ras mutations (2/12, 16%).
High prevalence of CIMP-high and K-ras mutations in G-LST, especially in the proximal colon, could strongly suggest that G-LST appearance is associated with a unique carcinogenic pathway.
侧向发育型肿瘤（LST）以沿结肠腔的浅表扩展为特征，最近已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鲜有报道。
共收集了205份散发性结直肠腺瘤组织（157份隆起型、23份颗粒型LST（G-LST）、12份扁平型LST（F-LST）以及13份直径小于1cm的扁平型）。通过检测p16、肿瘤甲基化（MINT）1、2、12和31位点的甲基化状态来确定CpG岛甲基化表型（CIMP）。还检测了K-ras密码子12和13的点突变。分析了宏观外观与CIMP状态或K-ras突变之间的关系。
在直径大于1cm的腺瘤中，与隆起型腺瘤（18/73，25%）相比，G-LST（14/23，61%）中更易观察到涉及2个或更多位点的CpG岛甲基化（CIMP高）（P = 0.002）。G-LST中K-ras突变的发生率（18/23，78%）显著高于隆起型腺瘤（18/73，25%）（P < 0.0001）。此外，位于近端结肠的G-LST中CIMP高和K-ras突变的发生率更高（分别为11/13，85%；以及12/13，92%）。相比之下，F-LST中CIMP高（1/12，8%）和K-ras突变（2/12，16%）的发生率较低。
G-LST中CIMP高和K-ras突变发生率高，尤其是在近端结肠，强烈提示G-LST的外观与独特的致癌途径相关。
