Abstract
BackgroundMetastasis is a major cause of failed colorectal cancer (CRC) treatment. While lung metastasis (LM) is observed in 10–15% of patients with CRC, the genetic mechanisms that cause CRC to metastasize to the lung remain unclear.MethodsIn this study, we employed whole exome sequencing (WES) of primary CRC tumors and matched isolated LM lesions to compare their genomic profiles. Comprehensive genomic analyses of five freshly frozen primary tumor lesions, five paired LM lesions, and matched non-cancerous tissues was achieved by WES.ResultsAn integrated analysis of somatic mutations, somatic copy number alterations, and clonal structures revealed that genomic alterations were present in primary and metastatic CRCs with various levels of discordance, indicating substantial levels of intertumor heterogeneity. Moreover, our results suggest that the founder clone of the primary tumor was responsible for the formation of the metastatic lesion. Additionally, only a few metastasis-specific mutations were identified, suggesting that LM-promoting mutations might be pre-existing in primary tumors.ConclusionsPrimary and metastatic CRC show intertumor heterogeneity; however, both lesions were founded by the same clone. These results indicate that malignant clones contributing to disease progression should be identified during the genetic prognosis of cancer metastasis.
Highlights
Metastasis is a major cause of failed colorectal cancer (CRC) treatment
These results indicate that malignant clones contributing to disease progression should be identified during the genetic prognosis of cancer metastasis
Tissue samples were fully ground with liquid nitrogen and the nuclei were suspended in extraction buffer (1 M sodium chloride, 100 mM Tris, and 50 mM EDTA [pH 8.0]) containing 2% sodium dodecyl sulfate (SDS) and proteinase K (2 mg/ml final concentration)
Summary
While lung metastasis (LM) is observed in 10–15% of patients with CRC, the genetic mechanisms that cause CRC to metastasize to the lung remain unclear. Colorectal cancer (CRC) is a leading cause of cancerrelated death worldwide and the number of patients being diagnosed with CRC is growing in China [1, 2]. Metastasis is a major cause of failed colorectal cancer (CRC) treatment. 50% of CRC patients that undergo radical resection of the primary tumor go on to develop metastatic disease, with the most common metastatic sites being the liver and lung [3, 4]. Cancer metastasis to distant organs is thought to occur via. The specific molecules involved in CRC LM have been investigated.
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