Biopolym. Cell. 2014; 30(2):129-134.
Molecular Biomedicine
Comparative analysis of epigenetic markers
in plasma and tissue of patients with colorectal cancer
- State Key Laboratory of Molecular and Cellular Biology
Institute of Molecular Biology and Genetics, NAS of Ukraine
150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680 - National Cancer Institute
33/43, Lomonosova Str., Kyiv, Ukraine, 03022 - Department of Microbiology, Tumor and Cell Biology,
Karolinska Institute
Nobels vag 5 171 65 Solna, Sweden
Abstract
Aim. The work is devoted to the development of less invasive tools for the colorectal cancer (CRC) screening. Methods. Q-PCR and methylation-specific PCR techniques were used in the current work. Results. We have shown that the levels of cell-free plasma DNA are higher in the CRC patients compared with the healthy donors (p < 0.01). Hypermethylation of APC, FHIT, LRRC3B and HIC1 genes was studied in the tumor and plasma samples of CRC patients. Two-stage verification for CRC screening was proposed. Conclusions. We proposed and tested a novel approach for CRC screening based on the determination of cell-free DNA and methylated DNA fragments in the plasma.
Keywords: colorectal cancer, cell-free DNA, DNA methylation, APC, FHIT, LRRC3B , HIC1
Full text: (PDF, in English)
References
[1]
Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010; 127(12):2893–917.
[2]
Rex DK, Bond JH, Winawer S, Levin TR, Burt RW, Johnson DA, Kirk LM, Litlin S, Lieberman DA, Waye JD, Church J, Marshall JB, Riddell RH; U.S. Multi-Society Task Force on Colorectal Cancer. Quality in the technical performance of colonoscopy and the continuous quality improvement process for colonoscopy: recommendations of the U.S. Multi-Society Task Force on Colorectal Cancer. Am J Gastroenterol. 2002; 97(6):1296–308.
[3]
Louis MA, Nandipati K, Astorga R, Mandava A, Rousseau CP, Mandava N. Correlation between preoperative endoscopic and intraoperative findings in localizing colorectal lesions. World J Surg. 2010; 34(7):1587–91.
[5]
Esteller M. CpG island hypermethylation and tumor suppressor genes: a booming present, a brighter future. Oncogene. 2002; 21(35):5427–40.
[6]
Kohler C, Barekati Z, Radpour R, Zhong XY. Cell-free DNA in the circulation as a potential cancer biomarker. Anticancer Res. 2011; 31(8):2623–8.
[7]
Kim M, Kim JH, Jang HR, Kim HM, Lee CW, Noh SM, Song KS, Cho JS, Jeong HY, Hahn Y, Yeom YI, Yoo HS, Kim YS. LRRC3B, encoding a leucine-rich repeat-containing protein, is a putative tumor suppressor gene in gastriccancer. Cancer Res. 2008; 68(17):7147–55.
[8]
Pichiorri F, Palumbo T, Suh SS, Okamura H, Trapasso F, Ishii H, Huebner K, Croce CM. Fhit tumor suppressor: guardian of the preneoplastic genome. Future Oncol. 2008; 4(6):815–24.
[9]
Dumitrescu RG. Epigenetic markers of early tumor development. Methods Mol Biol. 2012; 863:3–14.
[10]
Dehennaut V, Leprince D. Implication of HIC1 (Hypermethylated In Cancer 1) in the DNA damage response. Bull Cancer. 2009; 96(11):E66–72.
[11]
Kondratov AG, Stoliar LA, Kvasha SM, Gordiyuk VV, Zgonnyk YM, Gerashchenko AV, Vozianov AF, Rynditch AV, Zabarovsky ER, Kashuba VI. Methylation pattern of the putative tumor-suppressor gene LRRC3B promoter in clear cell renal cell carcinomas. Mol Med Rep. 2012; 5(2):509–12.
[12]
Li B, Wang B, Niu LJ, Jiang L, Qiu CC. Hypermethylation of multiple tumor-related genes associated with DNMT3b up-regulation served as a biomarker for early diagnosis of esophageal squamous cell carcinoma. Epigenetics. 2011; 6(3):307–16.
[13]
Kvasha S, Gordiyuk V, Kondratov A, Ugryn D, Zgonnyk YM, Rynditch AV, Vozianov AF. Hypermethylation of the 5'CpG island of the FHIT gene in clear cell renal carcinomas. Cancer Lett. 2008; 265(2):250–7.
[14]
Kristensen LS, Raynor MP, Candiloro I, Dobrovic A. Methylation profiling of normal individuals reveals mosaic promoter methylation of cancer-associated genes. Oncotarget. 2012; 3(4): 450–61.
[15]
Segditsas S, Sieber OM, Rowan A, Setien F, Neale K, Phillips RK, Ward R, Esteller M, Tomlinson IP. Promoter hypermethylation leads to decreased APC mRNA expression in familial polyposis and sporadic colorectal tumours, but does not substitute for truncating mutations. Exp Mol Pathol. 2008; 85(3):201–6.
[16]
Sinha R, Hussain S, Mehrotra R, Kumar RS, Kumar K, Pande P, Doval DC, Basir SF, Bharadwaj M. Kras gene mutation and RASSF1A, FHIT and MGMT gene promoter hypermethylation: indicators of tumor staging and metastasis in adenocarcinomatous sporadic colorectal cancer in Indian population. PLoS One. 2013; 8(4):e60142.
[17]
Tian XQ, Zhang Y, Sun D, Zhao S, Xiong H, Fang J. Epigenetic silencing of LRRC3B in colorectal cancer. Scand J Gastroenterol. 2009; 44(1):79–84.
[18]
Abouzeid HE, Kassem AM, Abdel Wahab AH, El-mezayen HA, Sharad H, Abdel Rahman S. Promoter hypermethylation of RAS SF1A, MGMT, and HIC-1 genes in benign and malignant colorectal tumors. Tumour Biol. 2011; 32(5):845–52.
[19]
Skrypkina IYa, Kondratov OG, Tsyba LO, Panasenko GV, Nikolaienko OV, Romanenko AM, Kolesnyk OO, Morderer DYe, Nekrasov KA, Kashuba VI, Vozianov SO, Shchepotin IB, Rynditch AV. Detection of cell-free DNA and gene-specific methylation in blood plasma of patients with renal and colon cancer. Nauka ta innovacii. 2012; 8(6):60–6.