Background: Seminoma is a malignant germ cell tumor that most commonly involves the testicles but may involve the mediastinum, the retroperitoneum, and other extra-gonadal sites as well. This study aims to investigate the somatic genomic landscape of seminoma. Methods: Data for a retrospective observational analysis of seminoma was acquired from the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) with clinical and genomic data from 2017 and beyond. Using the R and R Studio software (R 4.5.0), analyses for common somatic mutations and copy number alterations were run with a statistical significance ofp< 0.05. Results: The most mutated genes includedKIT(22.6%),KRAS(17.1%), andMTOR(5.1%), with significant copy number alterations inCDKN1B(17.2%),KRAS(14.7%),CCND2(10.3%), andH3F3C(9.8%). These suggest involvement within the KIT/RAS/MAPK and PI3K/AKT/mTOR (PAM) pathways for seminoma development. A novel finding within comparative evaluation ofPMS1andAMER1mutations were found in Black individuals. Additionally, our findings were consistent with a lower testicular cancer rate among individuals with African ancestry than European ancestry.BRD4mutations were found only in metastatic samples whileKMT2C,STAG2,ALK,AXL, andEGFRwere only found in primary samples, suggesting a possible association. Conclusions: This study provided a comprehensive molecular and genetic profiling of seminoma including key genetic alterations, affected pathways, and potential therapeutic strategies. Moreover, overlap between pathways and gene mutations provides the potential for alternative treatment options for seminoma via multiple pathways.
背景：精原细胞瘤是一种恶性生殖细胞肿瘤，最常见于睾丸，但也可能累及纵隔、腹膜后及其他性腺外部位。本研究旨在探讨精原细胞瘤的体细胞基因组特征。方法：通过美国癌症研究协会（AACR）的"基因组学证据肿瘤信息交换"（GENIE）项目获取2017年及以后的临床与基因组数据，对精原细胞瘤进行回顾性观察分析。使用R及R Studio软件（R 4.5.0）分析常见体细胞突变和拷贝数变异，统计显著性设定为p<0.05。结果：突变频率最高的基因包括KIT（22.6%）、KRAS（17.1%）和MTOR（5.1%），显著拷贝数变异涉及CDKN1B（17.2%）、KRAS（14.7%）、CCND2（10.3%）和H3F3C（9.8%）。这些发现提示KIT/RAS/MAPK和PI3K/AKT/mTOR（PAM）通路参与精原细胞瘤的发展。比较分析发现PMS1和AMER1突变在黑人个体中出现是新发现。此外，研究结果与非洲裔人群睾丸癌发病率低于欧洲裔人群的流行病学数据一致。BRD4突变仅见于转移样本，而KMT2C、STAG2、ALK、AXL和EGFR仅见于原发样本，提示可能存在特定关联。结论：本研究提供了精原细胞瘤的全面分子遗传学特征，包括关键遗传变异、受影响通路及潜在治疗策略。通路与基因突变的交叉作用为通过多通路联合治疗精原细胞瘤提供了新的可能性。
肿瘤(癌症)患者之家