RNF43 p.G659fs 通过 PI3K/AKT/mTOR 信号通路和 HLA-E 上调导致 MSI-high 结直肠癌中 NK 细胞功能障碍
RNF43 p.G659fs leads to natural killer cell dysfunction in MSI-high colorectal cancer through PI3K/AKT/mTOR signaling and HLA-E up-regulation.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
分子镶嵌：揭示同时性结直肠癌的异质性
英文原题：Molecular Mosaics: Unveiling Heterogeneity in Synchronous Colorectal Cancers.
查看英文原题
Molecular Mosaics: Unveiling Heterogeneity in Synchronous Colorectal Cancers.
分数与星级只用于站内排序 —— 不代表疗效、安全性或个人适用性。
研究概要
尽管同步癌症共享一个突变基因，但突变亚型不同。SCRC 表现出 5.1% 的 MSI 状态不一致率和体细胞突变变异的高不一致率。由于肿瘤间异质性可能影响靶向治疗反应，建议对 SCRC 患者的所有肿瘤进行分子分析。
研究思路结论见上方概要
目的
同时性结直肠癌（SCRCs）的分子特征仍未完全阐明，尽管其对靶向治疗选择具有重要意义。我们比较了SCRCs之间的分子特征和体细胞突变。
方法
这项回顾性研究（2012-2014年）纳入了98例连续接受手术切除的SCRC患者。对所有癌症病灶的分子特征进行了分析，包括微卫星不稳定性（MSI）和TIL（肿瘤浸润淋巴细胞）（TILs）。对9例至少有一个MSI-high（MSI-H）肿瘤患者的18个癌症样本进行了全外显子组测序（WES），以评估SCRC的肿瘤间异质性。
结果
12例患者至少有1个MSI-H肿瘤；5例显示MSI状态不一致。至少有1个MSI-H肿瘤的患者中，黏液腺癌发生频率和TIL密度高于仅有微卫星稳定肿瘤的患者。WES显示，除1例患者（6.5%）外，大多数同时性肿瘤在每个患者中共享的变异很少（0.09%-0.36%）。每个患者同时性肿瘤中BRAF、KRAS、NRAS和PIK3CA的一致率分别为66.7%、66.7%、66.7%和55.6%。
展开英文摘要原文
PURPOSE
Molecular characteristics of synchronous colorectal cancers (SCRCs) remain incompletely elucidated, despite their importance in targeted therapy selection. We compared the molecular characteristics and somatic mutations between SCRCs.
MATERIALS AND METHODS
This retrospective study (2012-2014) included 98 consecutive patients with surgically resected SCRCs. Molecular characteristics, including microsatellite instability (MSI) and tumor-infiltrating lymphocytes (TILs), were analyzed for all cancer lesions. The intertumoral heterogeneity of SCRCs was evaluated using whole-exome sequencing (WES) for 18 cancers from nine patients with at least one MSI-high (MSI-H) tumor.
RESULTS
Twelve patients had at least one MSI-H tumor; five showed discordant MSI status. Mucinous adenocarcinoma frequency and TIL density were higher in patients with at least one MSI-H tumor than in those with only microsatellite-stable tumors. WES revealed that, except one patient (6.5%), most synchronous cancers shared few variants in each patient (0.09%-0.36%). The concordance rates for BRAF, KRAS, NRAS, and PIK3CA, in synchronous cancers from each patient were 66.7%, 66.7%, 66.7%, and 55.6%, respectively.
CONCLUSION
Although synchronous cancers shared a mutated gene, the mutation subtypes differed. SCRCs exhibited 5.1% MSI status discordance rate and a high discordance rate in somatic mutational variants. As intertumoral heterogeneity may affect the targeted therapy response, molecular analysis of all tumors is recommended for patients with SCRCs.
论文信息
- 作者
- Lee HG、Kim Y、Kim MJ、Kim YW、Jun SY、Kim D、Park IJ、Hong SM
- 第一作者单位
- Division of Colon and Rectal Surgery, Department of Surgery, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.South Korea
- 通讯作者单位
- Department of Pathology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.South Korea
- 期刊
- Cancer research and treatment2026 Jan
- 原文标识
- PubMed 39973140 · DOI 10.4143/crt.2024.947
在 PubMed 查看 → 出版商原文（DOI） 全文 PDF（PMC）· 可下载 治疗专题与资料阅读指南 资料来源与翻译说明 报告译文或资料问题 →