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Left-Sided Early-Onset vs Late-Onset Colorectal Carcinoma: Histologic, Clinical, and Molecular Differences.

左侧早发型大肠癌和迟发型大肠癌的比较:组织学 、临床和分子的差异

Pilozzi E,Maresca C,Duranti E,Giustiniani MC,Catalanotto C,Lucarelli M,Cogoni C,Ferri M,Ruco L,Zardo G

Abstract

Carcinomas of the left colon represent a neoplasm of older patients (late onset), but epidemiologic evidence has been showing an increasing incidence in patients 50 years or younger (early onset). In this study, we investigate pathologic and molecular features of early- and late-onset carcinoma of the left colon.
We selected 22 patients 50 years or younger and 21 patients 70 years or older with left-sided colorectal carcinoma (CRC). All samples were evaluated for pathologic features, microsatellite instability, and KRAS and BRAF mutations. Moreover, both groups were analyzed to identify CpG island methylator phenotype features and assessed with restriction landmark genome scanning (RLGS) to unveil differential DNA methylation patterns.
Early-onset patients had advanced pathologic stages compared with late-onset patients (P = .0482). All cases showed a microsatellite stable profile and BRAF wild-type sequence. Early-onset patients (43%) more frequently had mutations at KRAS codon 12 compared with late-onset patients (14%) (P =.0413). RLGS showed that patients younger than 50 years who had CRC had a significantly lower percentage of methylated loci than did patients 70 years or older (P = .04124), and differential methylation of several genomic loci was observed in the two groups.
Our results suggest that left-sided CRCs may present differential patterns of aberrant DNA methylation when they are separated by age.

摘要

左侧结肠癌是老年患者(晚发型)的一种肿瘤,但流行病学证据显示在50岁或更年轻的患者(早发型)中有增加的趋势。在这项研究中,我们研究了早发和晚发型左侧结肠癌的病理和分子特征。
我们选择了22例50岁或更年轻的患者、21例70岁或70岁以上有左侧大肠癌(CRC)的患者。所有的样本均评价病理特征、微卫星不稳定性及KRAS和BRAF的突变。此外,两组进行分析,识别CpG岛甲基化的表型特征,并行基因组限制性酶切扫描法评估以揭示DNA甲基化模式的差异。
与迟发型患者相比,早发病理分级更高(P=0.0482)。所有病例显示微卫星稳定和BRAF野生型序列。与迟发型患者(14%)相比,早发型的患者(43%)更频发KRAS12密码子的突变(P=0.0413)。RLGS显示,年龄小于50岁的左半结肠癌患者甲基化位点百分比显着低于70岁及其以上的患者(P=0.04124),在两组中观察到部分基因位点的甲基化差异。
我们的研究结果表明,依据年龄划分时,左侧大肠癌的DNA甲基化异常具有不同的模式。

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