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免疫检查点抑制剂治疗短串联重复突变非典型模式的微卫星不稳定阳性胰腺腺癌失败。

Failure of immune checkpoint inhibitors for microsatellite instability-positive pancreatic adenocarcinoma with atypical pattern of short tandem repeat mutation.

机构信息

Clinical Hospital 2, MEDSI, Moscow, 119071, Russia.

OncoAtlas LLC, Moscow, 119049, Russia.

出版信息

Immunotherapy. 2024;16(13):853-858. doi: 10.1080/1750743X.2024.2376516. Epub 2024 Jul 23.

DOI:10.1080/1750743X.2024.2376516
PMID:39041702
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11457661/
Abstract

Microsatellite instability (MSI) is an important biomarker in cancer. While routine methods can detect MSI in certain tumor types, in other tumor types the results may be incorrect due to differences in the MSI loci pattern. Here, we report the case of a patient with pancreatic adenocarcinoma, with confirmed MSI by two independent next-generation sequencing tests, but not by routine methods, who had progression on pembrolizumab. Comparison of the patient's MSI loci patterns with MSI+ colorectal adenocarcinoma samples showed a lower fraction of unstable loci, low resolution of a second peak in the repeat length spectrum of unstable short tandem repeats in the patient's sample, and a lower length of indels (3.7 vs 4.5 base pairs,  < 0.01).

摘要

微卫星不稳定性(MSI)是癌症的一个重要生物标志物。虽然常规方法可以检测某些肿瘤类型中的 MSI,但在其他肿瘤类型中,由于 MSI 基因座模式的差异,结果可能不正确。在这里,我们报告了一例胰腺腺癌患者的病例,该患者通过两种独立的下一代测序试验证实存在 MSI,但常规方法检测不到,并且对 pembrolizumab 治疗有进展。将患者的 MSI 基因座模式与 MSI+结直肠腺癌样本进行比较,结果显示不稳定基因座的比例较低,患者样本中不稳定短串联重复序列重复长度谱中的第二个峰分辨率较低,插入缺失的长度也较低(3.7 对 4.5 个碱基对,<0.01)。

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本文引用的文献

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Pan-Cancer Prevalence of Microsatellite Instability-High (MSI-H) Identified by Circulating Tumor DNA and Associated Real-World Clinical Outcomes.基于循环肿瘤 DNA 识别的泛癌种微卫星不稳定高(MSI-H)的流行情况及其与真实世界临床结局的相关性。
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A scoping review and meta-analysis on the prevalence of pan-tumour biomarkers (dMMR, MSI, high TMB) in different solid tumours.一项关于不同实体瘤中泛肿瘤生物标志物(错配修复缺陷、微卫星高度不稳定、肿瘤突变负荷高)患病率的范围综述和荟萃分析。
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Microsatellite instability profiles of gastrointestinal cancers: comparison between non-colorectal and colorectal origin.胃肠道癌症的微卫星不稳定性概况:非结直肠癌起源与结直肠癌起源的比较
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MutationalPatterns: the one stop shop for the analysis of mutational processes.突变模式:分析突变过程的一站式商店。
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J Immunother Cancer. 2022 Jan;10(1). doi: 10.1136/jitc-2021-003312.
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Comparison of microsatellite instability detection by immunohistochemistry and molecular techniques in colorectal and endometrial cancer.免疫组织化学和分子技术检测结直肠癌和子宫内膜癌微卫星不稳定性的比较。
Sci Rep. 2021 Jun 18;11(1):12880. doi: 10.1038/s41598-021-91974-x.
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