Low somatic K-ras mutation frequency in colorectal cancer diagnosed under the age of 45 years
Low somatic K-ras mutation frequency in colorectal cancer diagnosed under the age of 45 years
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DOI：
10.1016/j.ejca.2006.02.023
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发表时间：
2006-07-01
影响因子：
8.4
通讯作者：
Southey, Melissa C.
中科院分区：
文献类型：
--
作者：
Alsop, Kathryn;Mead, Leeanne;Southey, Melissa C.
K-ras基因体细胞突变是结直肠癌发生的常见事件，但其与发病年龄的关系尚未得到广泛研究。在这项研究中，我们分析了45岁以前诊断的结直肠癌的人群研究中的肿瘤，这些病例先前已经筛查了生殖系错配修复基因突变和微卫星不稳定性。我们使用显微解剖和测序方法在101例早发性结直肠癌中寻找密码子12、13和61的体细胞K-ras突变。检测到6个（6%）体细胞K-ras突变; 5个在密码子12（4个G > T转换和1个G > A），1个在密码子13（G > A转换）。在微卫星稳定肿瘤中鉴定了所有密码子12突变，在MSI高肿瘤中鉴定了密码子13突变。4例K-ras基因突变患者无结直肠癌家族史，2例有结直肠癌家族史。目前尚不清楚hMSH 2、hMLH 1、hMSH 6或hPMS 2是否携带生殖系突变。与其在大肠癌中的重要作用相比，体细胞K-ras突变在早发性大肠癌发生中的作用似乎是次要的。晚期癌症的发病年龄。(c)2006爱思唯尔有限公司保留所有权利。
Somatic mutation of K-ras is known to be a common event in colorectal cancer tumourigenesis however its association with age at onset has not been widely explored. in this study, we have analyzed tumours from a population-based study of colorectal cancer diagnosed before the age of 45 years, in which cases had been previously screened for germ-line mismatch repair gene mutations and for microsatellite instability. We used a micro-dissection and sequencing approach to search for somatic K-ras mutations in codons 12, 13 and 61 in 101 early-onset colorectal cancers. Six (6%) somatic K-ras mutations were detected; five in codon 12 (4 G > T transitions and 1 G > A) and one in codon 13 (G > A transition). All codon 12 mutations were identified in microsatellite stable tumours and the codon 13 mutation was identified in a MSI-high tumour. Four cases with K-ras mutations had no reported family history of colorectal cancer and two had some family history of colorectal cancer. None were known to carry a germ-line mutation in hMSH2, hMLH1, hMSH6 or hPMS2.The role of somatic K-ras mutations in early-onset colorectal cancer carcinogenesis appears to be minor, in contrast to its significant role in colorectal. cancer of later age of onset. (c) 2006 Elsevier Ltd. All rights reserved.