p53 mutation is common in microsatellite stable, BRAF mutant colorectal cancers
p53 mutation is common in microsatellite stable, BRAF mutant colorectal cancers
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DOI：
10.1002/ijc.26175
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发表时间：
2012-04-01
影响因子：
6.4
通讯作者：
Whitehall, Vicki L. J.
中科院分区：
文献类型：
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作者：
Bond, Catherine E.;Umapathy, Aarti;Whitehall, Vicki L. J.
大多数锯齿状通路结直肠癌存在BRAF癌基因突变，表现为CpG岛甲基化表型(CIMP)。这些癌症中有一半有微卫星不稳定性(MSI)和良好的预后。在缺乏MSI(微卫星稳定，MSS)的情况下，BRAF突变与预后特别差有关。传统的途径癌是BRAF野生型。P53基因突变是一种常见的肿瘤类型，且与晚期肿瘤密切相关。因此，我们假设P53突变在MSS/BRAF突变的结直肠癌中很常见。对1,081例结直肠癌进行BRAF突变筛查，以确定两个BRAF突变研究组(MSI：n=77；Mss：n=69)和一个BRAF野生型对照组(n=10 1)。用高分辨熔融分析筛选P53突变，用定量甲基化特异性聚合酶链式反应对CIMP和MGMT甲基化进行分类。分子数据与患者的年龄、性别、肿瘤部位和分期进行比较。突变型P53基因突变频率(40.6%，28/69)明显高于突变型癌(13/77，16.9%)，但与野生型癌(47/101，46.5%)相比差异无统计学意义(P>0.0001)。突变型癌中CIMP的发生率(55.3%)低于突变型癌(75.9%，41/54)，但高于野生型癌(3/85，3.5%)(p<；0.0001)。MSS/BRAF突变癌更常见于近端(38/54，70.3%)，但在患者年龄、性别分布和发病时的分期方面与MSS/BRAF野生型癌相似。MSS/BRAF突变的肿瘤具有锯齿状和传统的结直肠癌发生途径的分子和临床特征。
The majority of serrated pathway colorectal cancers have mutation of the BRAF oncogene and display the CpG island methylator phenotype (CIMP). Half these cancers have microsatellite instability (MSI) and an excellent prognosis. In the absence of MSI (microsatellite stable, MSS), BRAF mutation has been associated with a particularly poor prognosis. Traditional pathway cancers are BRAF wild type. Mutation of p53 is common and this correlates with advanced stage. We therefore hypothesized that p53 mutation would be common in MSS/BRAF mutant colorectal cancer. One thousand and eighty-one colorectal cancers were screened for BRAF mutation to identify two BRAF mutant study groups (MSI: n = 77; MSS: n = 69) and a BRAF wild type control group (n = 101). These were screened for p53 mutation by high resolution melt analysis and classified for CIMP and MGMT methylation by quantitative methylation specific PCR. Molecular data were compared to patient age, gender, tumor location and stage. p53 was mutated significantly more frequently in MSS/BRAF mutant (28/69, 40.6%) compared to MSI/BRAF mutant cancers (13/77, 16.9%), but this mutation rate did not differ from MSS/BRAF wild type cancers (47/101, 46.5%)(p < 0.0001). CIMP was less common in MSS/BRAF mutant (26/47, 55.3%) compared to MSI/BRAF mutant cancers (41/54, 75.9%), but was more common than in MSS/BRAF wild type cancers (3/85, 3.5%) (p < 0.0001). MSS/BRAF mutant cancers were more commonly proximal (38/54, 70.3%), but were similar to MSS/BRAF wild type cancers in terms of patient age, gender distribution and stage at presentation. MSS/BRAF mutant cancers share molecular and clinical features of both the serrated and traditional pathways of colorectal tumorigenesis.