Jackson Jamaal C, Sanchez Darren, Joon Aron Y, Estecio Marcos R, Johns Andrew C, Shah Amishi Y, Campbell Matthew, Ward John F, Pisters Louis L, Guo Charles C, Zhang Miao, Zacharias Niki M, Tu Shi-Ming
Department of Urology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
Cells. 2025 Apr 30;14(9):658. doi: 10.3390/cells14090658.
Germ cell tumors of the testis (GCTs) provide an ideal tumor model to investigate the cellular versus genetic origin of cancers. In this single institutional study, we evaluated 38 patients with bilateral GCT, including tumors that occurred simultaneously (synchronous) and those occurring at different times (metachronous). For nine of these patients, DNA was isolated from the right and left GCT to determine the genomic and epigenetic differences between tissues using whole-exome sequencing (WES) and reduced representation bisulfite sequencing (RRBS). We found that seminomas and non-seminomas are molecularly distinct based on DNA methylation and not due to synchronous or metachronous disease. In addition, we did not observe conservation of genetic mutations in right and left GCT in either synchronous or metachronous disease. Our data suggest a cellular origin for bilateral GCT.
睾丸生殖细胞肿瘤(GCTs)为研究癌症的细胞起源与基因起源提供了一个理想的肿瘤模型。在这项单机构研究中,我们评估了38例双侧GCT患者,包括同时发生(同步)和在不同时间发生(异时)的肿瘤。对于其中9例患者,从右侧和左侧GCT中分离DNA,使用全外显子组测序(WES)和简化代表性亚硫酸氢盐测序(RRBS)来确定组织之间的基因组和表观遗传差异。我们发现,精原细胞瘤和非精原细胞瘤在分子水平上基于DNA甲基化存在差异,而非由于同步或异时疾病。此外,在同步或异时疾病中,我们均未观察到右侧和左侧GCT之间存在遗传突变的一致性。我们的数据表明双侧GCT起源于细胞。