Colorectal cancer is the second most common cancer and the second leading cause of cancer related death in men and women in Germany according to the Robert Koch Institute. The leading cause for cancer related mortality is the development of metastasis.

In our study, we aim to identify novel regulators of the metastatic process in colorectal cancer. To this end we employed next generation whole genome sequencing of resected tissues from patients with metastatic colorectal cancer. In particular, we sequenced samples from primary tumor, corresponding normal colon mucosa, metastasis and normal tissue from the metastatic site. The DNA from one patient was thereby sequenced on two different platforms, one being Illumina HiSeq the other Complete Genomics (CG). Additionally, we sequenced the transcriptome of this patient to correlate mRNA expression with genetic aberrations. This abstract focusses on the first results regarding metastatic aberrations.

The average read coverage for the samples sequenced with the Illumina platform was between 50-60x and for the samples sequenced with CG between 105-135x. In total 3607 SNVs were identified in coding regions in the metastasis with both platforms, 40 of these were in exonic regions and classified as high confidence with both platforms.

We also sequenced samples from an additional two patients on one sequencing platform each. One of the patients also presented with liver metastasis, the other one with a lung metastasis. These data were also compared to the data from the first patient to identify possible common aberrations as well as possible differences between the different metastatic sites. We identified several copy number changes occurring in the same chromosomal regions in different patients. Similarly, several genes affected by SNVs were common in two of the patients, while only high confidence APC mutations were common to all three patients. Seven additional genes were affected by high confidence SNVs in the two patients sequenced using the CG platform and three on the Illumina platform, two of which have not yet been characterized in the context of cancer or metastasis.

Citation Format: Christine Hauser, Anna Shavinskaya, Barbara Hutter, Mohammed Abba, Olga Tkachenko, Peter Lichter, Roland Eils, Benedikt Brors, Heike Allgayer. Whole genome profiling to identify novel metastasis regulators in colorectal cancer. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2010. doi:10.1158/1538-7445.AM2013-2010