转位相关的肉瘤中二次遗传变化的谱和临床影响
Hsin-Yi Chang1,2, William Tap3, Emily Slotkin4
1Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
JCO precision oncology
|October 30, 2025
概括
瘤性二次遗传变异 (SGA) 在转位关联瘤 (TAS) 中很常见,与较高的瘤突变负担和特定亚型 (如尤文瘤和单一纤维瘤) 的更差生存率相关.
科学领域:
- 对萨尔科马的基因组分析
- 癌症基因组学 癌症基因组学
- 在瘤学瘤学.
背景情况:
- 转位相关瘤 (TAS) 是一组多样化的瘤.
- 通常,TAS是由瘤性融合驱动的,导致稳定的基因组和低瘤突变负担 (TMB).
- 二次遗传变化 (SGA) 是罕见的,但可以影响临床行为.
研究的目的:
- 综合研究不同TAS基因型的致癌性/可能致癌性SGA的临床影响.
- 调查632个TAS的基因组景观,包括尤宁肉瘤,脱塑性小圆细胞肉瘤,单一纤维性瘤和突肉瘤.
- 为了将副本数的变化与患者的存活率相关联.
主要方法:
- 通过针对性下一代测序,对632个跨常见基因型的TAS进行了分析.
- 基因融合伙伴的确认和基因水平和手臂水平拷贝数变化的评估.
- 基因组改变与无进展生存率 (PFS) 和疾病特异性生存率的相关性.
主要成果:
- 瘤性SGA在51%的患者中被发现,最常见的是状脂肪肉瘤 (88%).
- 患有瘤性SGA的患者表现出更高的TMB,并且与转移和/或在尤文肉瘤,SFT,SS和MLS中更糟糕的PFS有关.
- TP53突变是最常见的致癌性SGA,与SFT和ES的较差结果有关;TERT促进器突变也与SFT和MLS的转移有关.
结论:
- 瘤性SGA在TAS中普遍存在,并显著影响患者的存活率.
- TP53和TERT促进体突变是关键的SGA,与特定TAS基因型中的侵略性临床行为和转移有关.
- 这项研究强调了评估TAS患者预后分层的SGA的重要性.
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