Improved marker combination for detection of de novo genetic variation and aberrant DNA in colorectal neoplasia
Improved marker combination for detection of de novo genetic variation and aberrant DNA in colorectal neoplasia
复制标题
DOI：
10.1373/clinchem.2007.070896
复制
发表时间：
2006-12-01
影响因子：
9.3
通讯作者：
Shuber, Anthony
中科院分区：
文献类型：
--
作者：
Kann, Lisa;Han, James;Shuber, Anthony
背景资料：散发性结直肠癌（CRC）的遗传异质性使得遗传标记物和序列变异检测技术的选择对筛查检测的性能至关重要。我们之前已经描述了由KRAS、APC、TP 53和BAT-26（V1）中的22种已知变体组成的CRC检测的有效性。我们引入了一种新的标记物制剂（V2），包括检测APC、PIK 3CA和CTNNB 1中的从头变异，SMARCA 3和Vim中的高甲基化序列，以及BRAF中的单碱基变异。我们比较了V1和V2标记检测异常DNA在结直肠neoplasia.Methods的能力：V1和V2标记制剂被用来分析144结直肠组织，样本包括50癌前腺瘤，94癌，和11非病理组织。V1分析由22个VI变体的单碱基延伸分析组成。V2分析包括APC突变簇区、PIK 3CA第9和20外显子、CTNNB 1第3外显子的DNA扫描、BRAE Val 600 Glu置换分析、Vim和SMARCA 3甲基化特异性PCR分析。结果：V2标记物对肿瘤的敏感性明显高于V1标记物（分别为93.6%和72.3%; P = 0.0002）和腺瘤（分别为92.0%和62.0%; P = 0.0006）。没有一个非病理样本是阳性的任何marker.Conclusions：我们证明了一种新的标记物配方（V2）检测异常的DNA在CRC和癌前腺瘤肿瘤组织的灵敏度提高。(c)2006年美国临床化学协会。
Background: The genetic heterogeneity of sporadic colorectal cancer (CRC) makes the choice of genetic markers and sequence variation-detection technologies critical to the performance of screening assays. We have previously described the effectiveness of a CRC assay composed of 22 known variants in KRAS, APC, TP53, and BAT-26 (V1). We introduce a new marker formulation (V2) that includes detection of de novo variation in APC, PIK3CA, and CTNNB1, hypermethylated sequences within SMARCA3 and VIM, and a single-base variation within BRAF. We compared the abilities of the V1 and V2 markers to detect aberrant DNA in colorectal neoplasias.Methods: V1 and V2 marker formulations were used to analyze 144 colorectal tissue, samples comprising 50 precancerous adenomas, 94 carcinomas, and 11 nonpathologic tissues. V1 analysis consisted of single-base extension analysis of the 22 VI variants. V2 analysis consisted of DNA scanning of the APC mutation cluster region, PIK3CA exons 9 and 20, CTNNB1 exon 3, analysis for the BRAE Val600Glu substitution, and methylation-specific PCR analysis of VIM and SMARCA3.Results: The V2 marker formulation had significantly higher sensitivity than the V1 markers for carcinomas (93.6% and 72.3%, respectively; P = 0.0002) and adenomas (92.0% and 62.0%, respectively; P = 0.0006). None of the nonpathologic samples were positive for any marker.Conclusions: We demonstrate improved sensitivity of a new marker formulation (V2) to detect aberrant DNA in CRC and precancerous adenoma tumor tissues. (c) 2006 American Association for Clinical Chemistry.