Chen Xingyao, Ligumsky Hagai, Ambrose Charlie, Sibrian Denisse, Tran Brian, Arif Daoud, Castellanos Olga, Kessner Darren, Luo Hanyi, Ubale Mukta, Coleman Abigail, Mahaganapathy Vaidhyanathan, Jönsson Thomas J, Basho Reva K, Lee Jerry S H, Matasci Naim, Agus David B
Ellison Medical Institute, Los Angeles, CA, USA.
Providence Saint John's Cancer Institute, Santa Monica, CA, USA.
Sci Rep. 2025 Jun 11;15(1):18397. doi: 10.1038/s41598-025-01690-z.
Cancer initiation occurs when a cell acquires and accumulates mutations in genes involved in the regulation of cell processes: each cell division throughout a person's life introduces novel mutations in the cells' DNA and under normal circumstances, the body is primed to prevent those from leading to cancer. Occasionally, a subset of those mutations escapes those safeguards and might eventually result in the emergence of the disease. To understand the dynamics of accumulation of somatic mutations, we have performed longitudinal whole genome sequencing of DNA obtained from whole blood from healthy individuals and cancer patients using Oxford Nanopore Technologies' Long Read Sequencing. Here we show that the number of somatic single nucleotide variants detected increases with their age and that for specific mutational processes, changes can be detected within months. We computed aggregated metrics for unique participants at each timepoint across types of variants (based on single based substitution molecular signatures) and identified patterns of change both over an individual's lifespan (age) and over the sampling period (months). This study showcases the suitability of long read sequencing of blood DNA for detecting coarse-grained differences over time and enable future development of "state of the system" personalized prevention programs.
人一生中的每次细胞分裂都会在细胞DNA中引入新的突变，在正常情况下，身体会做好准备防止这些突变导致癌症。偶尔，这些突变中的一部分会逃脱这些保护机制，最终可能导致疾病的出现。为了了解体细胞突变的积累动态，我们使用牛津纳米孔技术公司的长读长测序对从健康个体和癌症患者全血中获取的DNA进行了纵向全基因组测序。我们在此表明，检测到的体细胞单核苷酸变异数量随年龄增长而增加，对于特定的突变过程，可在数月内检测到变化。我们针对各时间点的独特参与者，根据变异类型（基于单碱基替换分子特征）计算了汇总指标，并确定了个体寿命期间（年龄）和采样期间（数月）的变化模式。本研究展示了血液DNA长读长测序在检测随时间的粗粒度差异方面的适用性，并为未来“系统状态”个性化预防方案的开发提供了可能。
