PO.CL01.09 · 临床研究
亚洲子宫内膜癌循环肿瘤DNA的基因组分析：A-TRAIN研究
Genomic profiling of circulating tumor DNA in endometrial cancer in Asia: A-TRAIN study
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
背景：子宫内膜癌影响全球超过420,000名女性，其中约40%的病例发生在亚洲。近年来，子宫内膜癌通过分子分型得以更精确地分类，这改善了预后评估并指导了治疗策略。在本研究中，我们利用液体活检样本——循环肿瘤DNA（ctDNA）的全面基因组分析，鉴定了亚洲患者子宫内膜癌的分子亚型。
方法：这是一项由日本、马来西亚、菲律宾、中国台湾和泰国五家机构开展的亚洲多中心前瞻性观察性研究（NCT05099978，ClinicalTrials.gov）。符合入选条件的患者具有转移性或复发性子宫内膜癌的组织学诊断。基因组分析采用AmpliSeq HD定制panel（Thermo Fisher Scientific）进行，靶向23个基因（752个扩增子），使用AmpliSeq Designer设计，以覆盖与子宫内膜癌相关的基因及热点突变区域。该panel可鉴定：（1）以下基因的全长：ARID1A、ARID1B、B2M、CCNE1、CTCF、JAK1、PIK3R1、PTEN、RB1、RPL22、SMARCB1、SMARCA4和TP53；（2）以下基因的热点突变或区域：AKT1、BRAF、CTNNB1、ERBB2、KRAS、MET、MYC、PIK3CA、POLE和PPP2R1A。
结果：从2022年8月至2024年3月，共入组60例晚期子宫内膜癌患者，包括来自日本的44例、中国台湾的10例、马来西亚的3例、菲律宾的2例和泰国的1例。中位年龄为59岁（范围31至79岁）。大多数病例在液体活检时处于复发状态（36例；60.0%）。在治疗方面，10例（16.7%）受试者在液体活检前接受过放疗，33例（55%）患者在液体活检前接受过化疗。75.0%（45/60）的病例检测到基因组改变，每例中位基因组异常数为2个（范围0-12）。最常发生改变的基因为PTEN（n=20，33.3%）、TP53（n=19，31.7%）、PIK3CA（n=19，31.7%）和CTNNB1（n=14，23.3%）。CNV分析排除了18个同时具有低覆盖深度和低均一性、或仅低均一性的样本，最终共分析42例。8例患者检测到CNV：2例ERBB2扩增、2例PIK3CA扩增、2例MYC扩增和2例CCNE1扩增。
结论：在治疗开始前对液体样本进行全面基因组分析，可能有助于为晚期或复发性子宫内膜癌的亚洲患者指导个体化治疗策略。
查看英文原文 English abstract
Background: Endometrial cancer affects more than 420,000 women worldwide, with approximately 40% of cases occurring in Asia. Recently, endometrial cancer is now more precisely categorized through molecular subtyping, which has improved prognostic assessment and guided treatment strategies. In this study, we identified molecular subtypes of endometrial cancer in Asian patients using comprehensive genomic profiling of liquid biopsy samples, circulating tumor DNA (ctDNA).
Methods: This is an Asian multicenter prospective observational study conducted by five institutions in Japan, Malaysia, Philippines, Taiwan, and Thailand (NCT05099978, ClinicalTrials.gov). Eligible patients had histological diagnosis of endometrial cancer with metastatic or recurrent disease. Genomic profiling was conducted by AmpliSeq HD custom panel (Thermo Fisher Scientific), targeting 23 genes (752 amplicons), designed using AmpliSeq Designer to cover on genes and hotspot mutation regions associated with endometrial cancer. This panel can identify (1) full-length in following genes: ARID1A, ARID1B, B2M, CCNE1, CTCF, JAK1, PIK3R1, PTEN, RB1, RPL22, SMARCB1, SMARCA4 and TP53 , (2) hotspot mutation or region in following genes: AKT1, BRAF, CTNNB1, ERBB2, KRAS, MET, MYC, PIK3CA, POLE and PPP2R1A .
Results: From August 2022 to March 2024, a total of 60 patients with advanced endometrial cancer were enrolled, including 44 from Japan, 10 from Taiwan, 3 from Malaysia, 2 from Philippines, and 1 from Thailand. The median age was 59 (range, 31 to 79) years. Most cases were at relapse (36; 60.0%) at liquid biopsy. In terms of therapy, 10 (16.7%) of the subjects had received radiation prior to the liquid biopsy, and 33 (55%) of the patients had received chemotherapy prior to the liquid biopsy. Genomic alterations were detected in 75.0% (45/60), with a median number of 2 genomic abnormality per case (range, 0-12). The most frequently altered genes were PTEN (n=20, 33.3%), TP53 (n=19, 31.7%), PIK3CA (n=19, 31.7%) and CTNNB1 (n=14, 23.3%). CNV analysis excluded 18 samples with both low coverage depth and low uniformity, or low uniformity alone, resulting in a total of 42 cases analyzed. CNVs were detected in eight patients: 2 with ERBB2 amplification, 2 with PIK3CA amplification, 2 with MYC amplification, and 2 with CCNE1 amplification.
Conclusion: The comprehensive genomic profiling of liquid-based samples prior to treatment initiation may help guide personalized therapeutic strategies for Asian patients with advanced or recurrent endometrial cancer.
利益披露 Disclosure
H. Tamura, None..
R. Miki, None..
T. Sasaki, None.