Colorectal cancer (CRC) has been the second leading cause of cancer-related deaths due in part to a low compliance rate (<50%) of the current screening method, an invasive colonoscopy, resulting in failure of detecting cancer early in its curative stages. 20% of CRC cases are only detected once the cancer has spread to a distant site, drastically reducing the 5-year survival rate from 90% to 12%. In order to improve the success of early detection methods of CRC, we have focused on developing non-invasive, multi-biomarker detection assays designed to identify CRC-associated genetic alterations. We have previously demonstrated that urine contains circulation-derived low molecular weight (LMW) DNA (<300 bp), which suggests that LMW urine DNA could be used to detect CRC-associated genetic alterations. Using previously identified stool and serum-based biomarkers for CRC, we have developed a panel of potential CRC markers for early detection for use in a non-invasive urine DNA test. Our panel contains genetic mutations and epigenetic alterations of nine genes: mutations of KRAS codons 12/13 and BRAF V600E and aberrant hypermethylation of VIM, SEPT9, BMP3, NDRG4, CDKN2A, TFPI2, and MGMT. The proof-of-concept of a CRC urine DNA test was demonstrated in a small pilot study investigating mVIM as a biomarker for CRC in matched tissue-urine samples. This led to the development of a PCR-based approach to quantify these markers in a prevalidation study with blinded CRC samples to identify the specificity and sensitivity of these genetic mutations and epigenetic alterations. In a concordant study using this blinded CRC sample set, our panel of markers was used in an amplicon NGS-based study. Results from these two studies will be used to confirm the sensitivity and specificity of each marker for early detection of CRC.

Citation Format: Adam Winfield Clemens, Selena Lin, Surbhi Jain, Ying-Hsiu Su, Wei Song. Detection of colorectal cancer-associated genetic and epigenetic alterations in urine of patients with CRC. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 1561. doi:10.1158/1538-7445.AM2015-1561

©2015 American Association for Cancer Research.
2015