Abstract LB-047: Single-cell genomics reveals the genesis of cancer: copy number variation precedes single nucleotide variation

Abstract

Abstract Recent advances in single cell whole genome amplification methods, such as MALBAC [1], have allowed accurate determination of copy number variation (CNV) as well as single nucleotide variation (SNV) of a single cancer cell [2]. In a bulk tissue sample at an early stage of cancer development, detection of abnormal CNV is often difficult, especially when the number of cells with abnormal CNV is small. Single cell genomic analysis is essential in evaluating the relation, if any, between CNV and SNV. We have carried out for the first time single cell genomic analyses of colonoscopy biopsy at different adenoma stages. Some single cells in the Stage II adenoma have CNVs in the tumor suppresser gene APC (the copy number loss reduced from two to one) as well as SNVs in numerous cancer related genes. Interestingly, we found that while some single cells exhibited CNV reduction in APC without SNVs, all single cells with SNVs in COSMIC genes showed the CNV reduction in APC. Moreover we did not see a single cell that has SNVs but not CNVs in an adenoma. These data indicates that the CNV of APC precedes the SNVs in colon cancer development. Furthermore, we found that the single cells from the same adenoma exhibited CNV patterns reproducible among all the cells, indicating that these cells were derived from the same stem cell, in which CNVs resulted from double strand breaks that could not be repaired perfectly. Thus, we have established for the first time a correlation between SNVs and CNVs and propose that SNVs are generated as a consequence of abnormal CNVs in the genome. Therefore, our results could have a significant implication on the genesis of cancer. References (1) Zong, et al. Science 338: 1622-1626 (2012). (2) Ni et al. PNAS 110, 21083 (2013). Note: This abstract was not presented at the meeting. Citation Format: Sunney Xie, Lei Huang, Fei Ma, Jingran Wang, Shigang Ding, Fang Gu, Wenjing Wang, Jing Zhang. Single-cell genomics reveals the genesis of cancer: copy number variation precedes single nucleotide variation. [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 LB-047. doi:10.1158/1538-7445.AM2015-LB-047