在固体瘤中GNAS变异的分子和临床病理影响
Paul Johannet1, Somer Abdelfattah1, Callahan Wilde1
1Division of Solid Tumor Oncology, Department of Medicine, Memorial Sloan Kettering, New York, NY.
概括
GNAS突变与各种癌症的粘膜瘤有关. 这些GNAS突变瘤表现出转移的增加,治疗反应不佳,生存结果更差,突出显示了它们的临床意义.
科学领域:
- 在瘤学瘤学.
- 分子生物学分子生物学
- 遗传学 遗传学是一种遗传学.
背景情况:
- 粘膜瘤发育的分子基础在很大程度上是未知的.
- 在粘膜尾腺癌中,GNAS突变与转移负担和治疗耐药性有关.
研究的目的:
- 为了研究GNAS变异的泛癌临床病理学相关性.
- 在各种固体瘤中识别与粘膜瘤表型相关的瘤性GNAS变体.
主要方法:
- 分析了58,043名患者的固体瘤,这些瘤是通过Memorial Sloan Kettering-Integrated Mutation Profiling of Actionable Cancer Targets (IMPACT) 进行测序的.
- 进行全面的分子分析,比较GNAS突变和野生类型瘤.
- 在癌症基因组图谱队列中的基因表达模式的评估.
- 对转移性疾病进行倾向匹配的分队分析,以评估GNAS变异状态与腹膜转移的关联,治疗反应,无进展生存 (PFS) 和整体生存 (OS).
主要成果:
- 粘菌性瘤对瘤性GNAS变体进行了丰富,在小肠,宫,结直肠,胰腺,食管胃,肝胆和肠道神经内分泌癌症的1%以上发现.
- 转基因突变GNAS瘤具有保存的分子特征 (C-to-T突变高,无体积低),KRAS共突变频繁,TP53变异较少.
- 突变GNAS瘤与腹转移的增加 (OR 1.7) 相关,第一线系统治疗反应更差 (OR 2.2),PFS更短 (中位数5.6vs7.0个月),独立预测更差的OS (HR 1.25).
结论:
- 跨各种癌症的GNAS突变瘤共享一种由粘膜组织学特征的保存表型.
- 这种表型包括腹膜转移的增加,对一线全身疗法的反应减弱,以及较差的生存结果.
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