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在胃肠道癌症中MTAP变化的临床病理学特性
Gianluca Mauri1,2,3, Giorgio Patelli4,2,3, Laura Roazzi2,3
1IFOM ETS - The AIRC Institute of Molecular Oncology, Milan, Italy gianluca.mauri@unimi.it.
Journal of clinical pathology
|February 13, 2024
概括
甲基氨酸酸化酶 (MTAP) 损失发生在5-10%的胃肠癌中,主要发生在上部胃肠道类型中. 这种MTAP损失不会使患者的预后恶化,并且通常与CDKN2A/B损失有关.
科学领域:
- 在瘤学瘤学.
- 代谢酶研究 代谢酶研究
- 基因组学就是基因组学.
背景情况:
- 甲基氨酸酸化酶 (MTAP) 对于 purin 和 methionine 的新陈代谢至关重要.
- 在癌症中,MTAP基因拷贝数损失 (MTAP损失) 会产生对阿尔金因甲基转移酶5的依赖.
- 在胃肠道 (GI) 癌症中MTAP变化的作用在很大程度上是未被探索的.
研究的目的:
- 为了确定胃肠道癌症中MTAP变化的患病率.
- 调查与MTAP损失相关的临床病理特征.
- 评估MTAP在肠道癌症中的损失的预后影响.
主要方法:
- 癌症基因组图谱 (TCGA) 的分析和肠道癌症的真实世界队列.
- 下一代测序用于MTAP变化概况.
- 针对非损失MTAP变化的免疫组织化学和用于预后评估的病例控制研究.
主要成果:
- 最常见的变化是MTAP损失 (9.4%),通常与CDKN2A/B损失 (97.7%) 同时发生.
- 胆囊 (20.5%) 和胃食道 (12.7%) 癌症显示MTAP损失患病率最高.
- 在结直肠癌中,MTAP损失很少 (1.1%),突变更常见,但很少导致可操作的蛋白质损失.
结论:
- MTAP的变化影响了5-10%的胃肠道癌,主要是胆和胃食道类型.
- 在微卫星稳定,CDKN2A/B损失,上肠道癌症中,MTAP损失很常见.
- 大肠直肠癌的MTAP变异大多是不太可能产生药物敏感性的突变.
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