Abstract
SummaryCancer is an evolutionary disease, and there is increasing interest in applying tools from evolutionary biology to understand cancer progression. Restriction-site associated DNA sequencing (RADseq) was developed for the field of evolutionary genetics to study adaptation and identify evolutionary relationships among populations. Here we apply RADseq to study tumor evolution, which allows for unbiased sampling of any desired frequency of the genome, overcoming the selection bias and cost limitations inherent to exome or whole-genome sequencing. We apply RADseq to both human pancreatic cancer and zebrafish melanoma samples. Using either a low-frequency (SbfI, 0.4% of the genome) or high-frequency (NsiI, 6-9% of the genome) cutter, we successfully identify single nucleotide substitutions and copy number alterations in tumors, which can be augmented by performing RADseq on sublineages within the tumor. We are able to infer phylogenetic relationships between primary tumors and metastases. These same methods can be used to identify somatic mosaicism in seemingly normal, non-cancerous tissues. Evolutionary studies of cancer that focus on rates of tumor evolution and evolutionary relationships among tumor lineages will benefit from the flexibility and efficiency of restriction-site associated DNA sequencing.
Highlights
The characterization of cancer as an evolutionary process was reviewed by Peter Nowell four decades ago
Www.impactjournals.com/oncotarget a large disciplinary divide still exists between cancer biology and evolutionary biology, and potentially useful theoretical and experimental tools have yet to be applied across disciplines
Many studies of evolution in cancer are more limited by the number of individuals or tissues sampled than by the density of markers in the genome, and for these studies Restriction-site associated DNA sequencing (RADseq) will be an especially useful tool
Summary
The characterization of cancer as an evolutionary process was reviewed by Peter Nowell four decades ago. He hypothesized a stepwise progression of acquired variation and natural selection to explain the emergence and increasing aggressiveness of tumors [1]. Theory and tools from evolutionary biology have been applied to the field of cancer biology to understand the rates of accumulation of mutations in cellular lineages [5, 7], spatial and temporal patterns of intratumor heterogeneity [8,9,10], the timing and order of metastatic progression [11,12,13,14], and optimal strategies for therapeutic dosing and schedules [15,16,17]. Www.impactjournals.com/oncotarget a large disciplinary divide still exists between cancer biology and evolutionary biology, and potentially useful theoretical and experimental tools have yet to be applied across disciplines
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