Affiliation:
1. University of Southern California
2. Translational Genomics
3. Norris Comprehensive Cancer Center
Abstract
Abstract
Cancer is the second most common cause of death in children aged 1-14 years in the United States, with 11,000 new cases and 1,200 deaths annually. Pediatric cancers typically have lower mutational burden compared to adult-onset cancers; however, the epigenomes of pediatric cancer are highly altered with widespread DNA methylation changes. Currently, whole genome bisulfite sequencing (WGBS) is the most powerful tool for methylome evaluation, but it has been infrequently used to study pediatric cancers. In this we performed WGBS on 34 relapsed pediatric tumors, 13 patient-matched adjacent normal, and 17 patient-matched cell-free (cf)DNA samples from plasma, representing 11 pediatric tumor types. DNA methylation analysis of these cancers revealed differentially methylated regions common to multiple tumor types, which were also detectible in cfDNA and showed potential relevance in multiple adult cancer types. In addition, WGBS data was utilized to estimate copy number alterations (CNAs) and somatic mutations. We also found that tumor associated cfDNA methylation was more sensitive than detection of circulating CNAs and somatic mutations. The resultant pan-cancer cfDNA methylation signature has potential utility in minimal residual disease monitoring and warrants further investigation in both pediatric and adult cancer.
Publisher
Research Square Platform LLC
Reference84 articles.
1. Cancer Facts & Figures;Americanâ Cancerâ Society;Atlanta: American Cancer Society,2019
2. Cancer Treatment & Survivorship Facts & Figs. 2019–2021;Americanâ Cancerâ Society;Atlanta: American Cancer Society,2019
3. Overview and recent advances in the treatment of neuroblastoma;Whittle SB;Expert Rev Anticancer Ther,2017
4. Outcome for children with metastatic solid tumors over the last four decades;Perkins SM;PLoS One,2014
5. Methods of measurement for tumor mutational burden in tumor tissue;Melendez B;Transl Lung Cancer Res,2018