Abstract
Abstract
Background
Whole-genome doubling (WGD) is a common mutation in cancer. Various studies suggested that WGD is associated with a poor prognosis in cancer. However, the detailed association between WGD occurrence and prognosis remains unclear. In this study, we aimed to elucidate how WGD affects prognosis using sequencing data from the Pan-Cancer Analysis of Whole Genomes and The Cancer Genome Atlas.
Methods
Whole-genome sequencing data of 23 cancer types were downloaded from the PanCancer Analysis of Whole Genomes (PCAWG) project. We defined the WGD event in each sample using the WGD status annotated by the PCAWG. We used MutationTimeR to predict the relative timing of mutations and LOH to WGD, which were investigated the association with WGD and them. We also analyzed the association between the WGD-associated factors and patient prognosis.
Results
We detected that WGD is associated with several factors, e.g., loss of heterozygosity (LOH) length. Survival analysis using WGD-associated factors showed that longer LOH and LOH in chr17 were associated with poor prognosis in the samples with and without WGD. In addition to these two factors, samples without WGD showed that the number of mutations in tumor suppressor genes was associated with prognosis. Moreover, we explored genes associated with prognosis in both samples separately.
Conclusion
This study revealed that the prognosis-related factors in samples with and without WGD significantly differ. This study emphasizes the need for different treatment strategies for samples with and without WGD.
Publisher
Research Square Platform LLC