Buckley David N, Tew Ben Yi, Gooden Chris, Salhia Bodour
Department of Translational Genomics, Keck School of Medicine, University of Southern California, Los Angeles, CA, USA.
Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA, USA.
NPJ Precis Oncol. 2024 Jun 1;8(1):125. doi: 10.1038/s41698-024-00590-1.
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 1200 deaths annually. Pediatric cancers typically have lower mutational burden compared to adult-onset cancers, however, the epigenomes in pediatric cancer are highly altered, with widespread DNA methylation changes. The rarity of pediatric cancers poses a significant challenge to developing cancer-type specific biomarkers for diagnosis, prognosis, or treatment monitoring. In the current study, we explored the potential of a DNA methylation profile common across various pediatric cancers. To do this, we conducted whole genome bisulfite sequencing (WGBS) on 31 recurrent pediatric tumor tissues, 13 normal tissues, and 20 plasma cell-free (cf)DNA samples, representing 11 different pediatric cancer types. We defined minimal focal regions that were differentially methylated across samples in the multiple cancer types which we termed minimally differentially methylated regions (mDMRs). These methylation changes were also observed in 506 pediatric and 5691 adult cancer samples accessed from publicly available databases, and in 44 pediatric cancer samples we analyzed using a targeted hybridization probe capture assay. Finally, we found that these methylation changes were detectable in cfDNA and could serve as potential cfDNA methylation biomarkers for early detection or minimal residual disease.
癌症是美国1至14岁儿童中第二大常见死因，每年有11000例新发病例和1200例死亡。与成人癌症相比，儿童癌症的突变负担通常较低，然而，儿童癌症的表观基因组发生了高度改变，存在广泛的DNA甲基化变化。儿童癌症的罕见性给开发用于诊断、预后或治疗监测的癌症类型特异性生物标志物带来了重大挑战。在本研究中，我们探索了各种儿童癌症中常见的DNA甲基化谱的潜力。为此，我们对31个复发性儿童肿瘤组织、13个正常组织和20个血浆游离（cf）DNA样本进行了全基因组亚硫酸氢盐测序（WGBS），这些样本代表了11种不同的儿童癌症类型。我们定义了在多种癌症类型的样本中差异甲基化的最小局灶区域，我们将其称为最小差异甲基化区域（mDMRs）。在从公开可用数据库获取的506个儿童癌症样本和5691个成人癌症样本中，以及在我们使用靶向杂交探针捕获测定法分析的44个儿童癌症样本中，也观察到了这些甲基化变化。最后，我们发现这些甲基化变化在cfDNA中可检测到，并且可以作为早期检测或微小残留病的潜在cfDNA甲基化生物标志物。
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