林奇样综合征中 MMR 基因的肿瘤分析：结果解读相关的挑战。
Tumor analysis of MMR genes in Lynch-like syndrome: Challenges associated with results interpretation.
机构信息
Hereditary Cancer Program, Catalan Institute of Oncology, Molecular Mechanisms and Experimental Therapy in Oncology Program, Institut d'Investigació Biomèdica de Bellvitge - IDIBELL, L'Hospitalet de Llobregat, Spain.
Centro de Investigación Biomédica en Red de Cáncer (CIBERONC), Madrid, Spain.
出版信息
Cancer Med. 2024 Apr;13(7):e7041. doi: 10.1002/cam4.7041.
BACKGROUND
Up to 70% of suspected Lynch syndrome patients harboring MMR deficient tumors lack identifiable germline pathogenic variants in MMR genes, being referred to as Lynch-like syndrome (LLS). Previous studies have reported biallelic somatic MMR inactivation in a variable range of LLS-associated tumors. Moreover, translating tumor testing results into patient management remains controversial. Our aim is to assess the challenges associated with the implementation of tumoral MMR gene testing in routine workflows.
METHODS
Here, we present the clinical characterization of 229 LLS patients. MMR gene testing was performed in 39 available tumors, and results were analyzed using two variant allele frequency (VAF) thresholds (≥5% and ≥10%).
RESULTS AND DISCUSSION
More biallelic somatic events were identified at VAF ≥ 5% than ≥10% (35.9% vs. 25.6%), although the rate of nonconcordant results regarding immunohistochemical pattern increased (30.8% vs. 20.5%). Interpretation difficulties question the current utility of the identification of MMR somatic hits in the diagnostic algorithm of suspected LS cases.
背景
多达 70%的怀疑患有 MMR 缺陷肿瘤的林奇综合征患者在 MMR 基因中缺乏可识别的种系致病性变异，被称为林奇样综合征（LLS）。先前的研究报告了在可变范围内的 LLS 相关肿瘤中存在双等位基因体细胞 MMR 失活。此外，将肿瘤检测结果转化为患者管理仍然存在争议。我们的目的是评估在常规工作流程中实施肿瘤 MMR 基因检测相关的挑战。
方法
在这里，我们展示了 229 例 LLS 患者的临床特征。对 39 个可获得的肿瘤进行了 MMR 基因检测，并使用两种变异等位基因频率（VAF）阈值（≥5%和≥10%）分析了结果。
结果与讨论
在 VAF≥5%时比≥10%时发现了更多的双等位基因体细胞事件（35.9%比 25.6%），尽管免疫组织化学模式的不一致结果率增加（30.8%比 20.5%）。解释困难质疑了当前在疑似 LS 病例的诊断算法中识别 MMR 体细胞突变的实用性。
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