| Abstrak/Abstract |
Background: Intra-tumor heterogeneity can facilitate tumor evolution and may hold important prognostic and predictive value. The aim of our study was to assess heterogeneity in genomic copy number aberrations (CNA) in primary and metastatic lung tumor samples at the single cell level using low coverage single-cell whole genome sequencing (scWGS). Patient and methods: Single nuclei of five frozen tumor samples of a small cell lung cancer patient were flow sorted and used to generate scWGS libraries. AneuFinder was used to identify good quality cells (n=346, 54-82 cells/sample) and define CNAs. Results: The single cell libraries showed both shared and distinct CNA patterns. The merged CNA plots of all five tumor samples revealed patterns that were similar to those of the total tumor DNA derived array CGH-based plots. The degree of intra-tumor CNA heterogeneity was the highest in the primary tumor, whereas the lowest degree of heterogeneity was observed in the liver metastasis. The most distinct CNA pattern was observed for the liver metastasis cells, with disomy, trisomy, and tetrasomy of chromosome 11, trisomy of 18, disomy of 22, and pentasomy of Xp. A CNA pattern identical to that of the merged liver metastasis was observed for two out of 74 cells of the primary tumor and for five out of 72 cells of the adrenal gland metastasis. Cells with the liver metastasis specific CNA pattern were not found in the other primary tumor sample or in the lymph node metastasis. Conclusions: Using scWGS we showed a high degree of CNA heterogeneity in tumor samples derived from five distinct locations. We identified metastasis resembling cells in primary tumor and adrenal metastasis.
Copy number alterations assessed at the single-cell level revealed mono- and polyclonal seeding patterns of distant metastasis in a small cell lung cancer patient. |
