SEPT9 and SHOX2 DNA methylation status and its utility in the diagnosis of colonic adenomas and colorectal adenocarcinomas

被引:48
作者
Semaan, Alexander [1 ]
van Ellen, Anne [2 ]
Meller, Sebastian [2 ]
Bergheim, Dominik [2 ]
Branchi, Vittorio [1 ]
Lingohr, Philipp [1 ]
Goltz, Diane [2 ]
Kalff, Joerg C. [1 ]
Kristiansen, Glen [2 ]
Matthaei, Hanno [1 ]
Pantelis, Dimitrios [1 ]
Dietrich, Dimo [2 ]
机构
[1] Univ Bonn, Dept Gen Visceral Thorac & Vasc Surg, Sigmund Freud Str 25, D-53127 Bonn, Germany
[2] Univ Bonn, Inst Pathol, Sigmund Freud Str 25, D-53127 Bonn, Germany
关键词
SHOX2; SEPT9; Adenomas; Colorectal cancer; Methylation; Amplification; LUNG-CANCER; PERIPHERAL-BLOOD; PERFORMANCE; ASSAY; BIOMARKERS; PLASMA; GENE; CLASSIFICATION; COLONOSCOPY; EPIGENOME;
D O I
10.1186/s13148-016-0267-5
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Background: Colorectal cancer (CRC) appear to arise from precursor lesions in a well-characterized adenoma-carcinoma sequence. Significant efforts have been invested to develop biomarkers that identify early adenocarcinomas and adenomas with high-grade dysplasia, since these are believed to harbor a particularly high risk for malignant transition and thus require resection. Promoter methylation of SEPT9 and SHOX2 has been suggested as a biomarker for various solid malignant tumors. Hence, the present study aimed to test their biomarker potential in CRC and precursor lesions. Results: Assessment of promoter methylation of SEPT9 distinguished adenomas and CRC from controls as well as advanced from non-advanced adenomas (all p < 0.001). Correspondingly, SHOX2 methylation levels in adenomas and colorectal carcinomas were significantly higher compared to those in normal control tissues (p < 0.001). Histologic transition from adenomas to CRC was paralleled by amplification of the SEPT9 gene locus. Conclusions: SEPT9/SHOX2 methylation assays may help to distinguish colorectal cancer and adenomas from normal and inflammatory colonic tissue, as well as advanced from non-advanced adenomas. Further studies need to validate these findings before introduction in clinical routine.
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页数:10
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