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Colorectal cancer (CRC) is a significantly increasing cause of cancer mortality, being now the second most common malignancy in both genders. According to some sources, morbidity associated with summed cancers of the colon and rectum in the European Union population is even higher than morbidity associated with lung cancer or breast cancer [1]. Every year, more than 500,000 CRC deaths are noted worldwide. Thirty-five percent of newly diagnosed patients are in stage IV, i.e. a late stage of the disease with distant metastases [2]. Common metastatic sites of CRC include regional lymph nodes, the liver, the lungs and bones, whereas pancreatic metastases are rare. Secondary tumours account for only about 2% of all pancreatic malignancies [3]. A vast majority of patients with metastatic tumours within the pancreas also present with other distant metastases, and in this group, the only line of treatment is systemic palliative care. Nevertheless, there is a very small group of patients with an isolated metastatic tumour within the pancreas who may be referred for pancreatectomy, which may increase survival and positively affect prognosis. [3, 4].

Background Approximately 90% of colorectal cancer (CRC) deaths are caused by tumors ability to migrate into the adjacent tissues and metastase into distant organs. More than 40 genes have been causally linked to the development of CRC but no mutations have been associated with metastasis yet. To identify molecular basis of CRC metastasis we performed whole-exome and genome-scale transcriptome sequencing of 7 liver metastases along with their matched primary tumours and normal tissue. Multiple, spatially separated fragments of primary tumours were analyzed in each case. Uniformly malignant tissue specimen were selected with macrodissection, for three samples followed with laser microdissection. Results > 100 sequencing coverage allowed for detection of genetic alterations in subpopulation of tumour cells. Mutations in KRAS, APC, POLE, and PTPRT, previously associated with CRC development, were detected in most patients. Several new associations were identified, including PLXND1, CELSR3, BAHD1 and PNPLA6. Conclusions We confirm the essential role of inflammation in CRC progression but question the mechanism of matrix metalloproteinases activation described in other work. Comprehensive sequencing data made it possible to associate genome-scale mutation distribution with gene expression patterns. To our knowledge, this is the first work to report such link in CRC metastasis context.