PO.MD01.02 · 分子诊断与数据

IDH1/2 突变的泛癌种全景，聚焦非小细胞肺癌：来自 AACR GENIE 登记数据库的见解

Pan-cancer landscape of IDH1/2 mutations with a focus on non-small cell lung cancer: Insights from the AACR GENIE Registry

编号 4109 展板 14 时间 4/21 09:00–12:00 区域 Section 1 主讲 Zhaohui (Ann) Arter, MD

分会场 AACR Project GENIE: Genomic Characterization

查看 PDF 下载 PDF 🔒 查看 / 下载完整 PDF 需登录并开通下载套餐 · 查看套餐 / 开通 AACR 官方页面

作者与单位 Authors & Affiliations

Zhaohui L. Arter, Cathleen Park, Misako Nagasaka, Sai-Hong I. Ou

UCI Health, Orange, CA

摘要 Abstract

中文摘要

背景：IDH1 和 IDH2 突变是多种肿瘤类型的致癌驱动因素。它们在非小细胞肺癌（NSCLC）中的患病率、突变谱和共改变特征仍未完全明确。鉴于已有获批的 IDH1 和 IDH2 抑制剂，表征这些突变具有潜在的治疗意义。方法：我们查询了 AACR GENIE v18 数据库（n=250,018 个肿瘤样本），以评估 NSCLC 中 IDH1/2 突变频率、亚型分布、相关组织学类型、共突变及生存结局。结果：IDH1 和 IDH2 突变分别在 5,380 例（2.2%）和 2,761 例（1.1%）患者中被识别。IDH1 突变——主要为 R132H（50.4%）和 R132C（20.6%）——在胶质瘤（42.6%）、胆管癌（6.0%）、肺腺癌（4.8%）和黑色素瘤（4.4%）中富集。IDH2 突变——主要为 R140Q（20%）和 R172K（9.8%）——在 AML（20.3%）、结直肠癌（7.4%）和 NSCLC（5.9%）中最为常见。在 30,454 例 NSCLC 患者中，IDH1 和 IDH2 突变分别发生于 1.2% 和 0.7%。EGFR 共突变见于 83 例（21.8%）IDH1 突变型和 39 例（22%）IDH2 突变型 NSCLC。KRAS 共突变见于 170 例（44.5%）IDH1 突变型和 51 例（29%）IDH2 突变型 NSCLC（见表）。在主要致癌亚组中，IDH 共突变分别发生于 EGFR L858R 的 1.04%（IDH1）和 0.60%（IDH2）、EGFR E746_A750del 的 1.18% 和 0.13%，以及 KRAS G12C 的 2.01% 和 0.81%。在 1,846 例有可用生存数据的患者中，IV 期 KRAS G12C+/IDH1/2- 患者的中位总生存期（OS）为 14.7 个月，而 KRAS G12C+/IDH1/2+ 患者为 9.7 个月（P = 0.02）。结论：在 IV 期 KRAS G12C 突变型 NSCLC 中，IDH1/2 共突变与较短的中位 OS 相关。这些发现，连同 IDH1/2 与 EGFR 和 KRAS 的频繁共改变，值得进一步研究靶向及联合策略。表：NSCLC 中 IDH1/2 共改变特征 IDH1（n=366） IDH2（n=199） EGFR 共突变 83（21.8%） 39（22%） L858R / E746_A750del 19 / 18 11 / 2 KRAS 共突变 170（44.5%） 51（29%） G12C / G12V / G12D 62 / 28 / 24 25 / 15 / 4 G12A / G12F / G12S / G12R 10 / 2 / 2 / 1 2 / 2 / 1 / 1 其他 KRAS 变异 41 6

查看英文原文 English abstract

Background: IDH1 and IDH2 mutations are oncogenic drivers across several tumor types. Their prevalence, mutational spectrum, and co-alteration profiles in Non-Small Cell Lung Cancer (NSCLC) remain incompletely defined. Given the availability of approved IDH1 and IDH2 inhibitors, characterizing these mutations has potential therapeutic relevance. Methods: We queried the AACR GENIE v18 database (n=250,018 tumor samples) to assess IDH1/2 mutation frequency, subtype distribution, associated histologies, co-mutations and survival outcomes in NSCLC. Results: IDH1 and IDH2 mutations were identified in 5,380 (2.2%) and 2,761 (1.1%) patients, respectively. IDH1 mutations-primarily R132H (50.4%) and R132C (20.6%)-were enriched in gliomas (42.6%), cholangiocarcinoma (6.0%), lung adenocarcinoma (4.8%), and melanoma (4.4%). IDH2 mutations-mainly R140Q (20%) and R172K (9.8%)-were most frequent in AML (20.3%), colorectal cancer (7.4%), and NSCLC (5.9%). Among 30,454 NSCLC patients, IDH1 and IDH2 mutations occurred in 1.2% and 0.7%, respectively. EGFR co-mutations were found in 83 (21.8%) of IDH1- and 39 (22%) of IDH2-mutant NSCLC. KRAS co-mutations were seen in 170 (44.5%) of IDH1- and 51 (29%) of IDH2-mutant NSCLC (Table). Across major oncogenic subgroups, IDH co-mutations occurred in 1.04% (IDH1) and 0.60% (IDH2) of EGFR L858R, 1.18% and 0.13% of EGFR E746_A750del, and in 2.01% and 0.81% of KRAS G12C, respectively. Among 1,846 patients with available survival data, the median overall survival (OS) was 14.7 months for stage IV KRAS G12C+/IDH1/2- patients compared with 9.7 months for KRAS G12C+/IDH1/2+ (P = 0.02). Conclusions: In stage IV KRAS G12C-mutant NSCLC, IDH1/2 co-mutations were linked to shorter median OS. These findings, along with the frequent co-alterations of IDH1/2 with EGFR and KRAS, warrant further study of targeted and combination strategies. Table: IDH1/2 Co-Alterations in NSCLC Feature IDH1 (n=366) IDH2 (n=199) EGFR co-mutations 83 (21.8%) 39 (22%) L858R / E746_A750del 19 / 18 11 / 2 KRAS co-mutations 170 (44.5%) 51 (29%) G12C / G12V / G12D 62 / 28 / 24 25 / 15 / 4 G12A / G12F / G12S / G12R 10 / 2 / 2 / 1 2 / 2 / 1 / 1 Other KRAS variants 41 6

利益披露 Disclosure

Z. L. Arter, Jassen Independent Contractor. Catalyst Independent Contractor. Taiho Independent Contractor. Rigel Independent Contractor. C. Park, Jassen Independent Contractor. M. Nagasaka, AstraZeneca Independent Contractor. Daiichi Sankyo Independent Contractor. Novartis Independent Contractor. Eli Lilly Independent Contractor. Pfizer Independent Contractor. EMD Serono Independent Contractor. Genentech Independent Contractor. Mirati Independent Contractor. Takeda Independent Contractor. Janssen Independent Contractor. Blueprint Medicine Independent Contractor. Caris Life Sciences Independent Contractor. AnHeart Therapeutics Travel. MBrace Therapeutics Stock. S. I. Ou, Pfizer Independent Contractor. Janssen/JNJ Independent Contractor. Caris Life Sciences Independent Contractor. AnHeart Therapeutics Independent Contractor. Daiichi Sankyo Independent Contractor. Bristol-Myers Squibb Independent Contractor. Merus Independent Contractor. Avisotone Independent Contractor. Elevation Oncology Independent Contractor. MBrace Therapeutics Stock. Elevation Oncology Stock. Turning Point Therapeutics Stock. Nuvalent Stock. Eli Lilly Stock. Nuvation Bio Stock. BlossomHill Therapeutics Stock.

← 返回 AACR 2026 检索