韩国年轻患者多原发肿瘤的患者内基因组差异

Korean journal of clinical oncology Pub Date : 2025-08-01 Epub Date: 2025-08-31 DOI:10.14216/kjco.25359
Yoon Young Choi
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引用次数: 0

摘要

目的:多发原发肿瘤发生在同一个体,对精确肿瘤学提出了挑战,特别是在遗传性癌症综合征(如Lynch综合征)的背景下。虽然这些肿瘤可能源于共同的种系易感性,但尚不清楚它们是否也有共同的可用于治疗的体细胞改变。本研究旨在描述韩国年轻患者同步或异时性胃癌和结直肠癌之间体细胞基因组重叠的程度。方法:19例55岁前诊断为胃癌和结直肠癌的患者对福尔马林固定石蜡包埋肿瘤组织进行全外显子组测序。确定微卫星不稳定性(MSI)状态,评估种系错配修复(MMR)变异以确定Lynch综合征病例。分析了体细胞突变、突变特征和拷贝数改变,以量化个体患者的肿瘤间基因组相似性。结果:在分析的37例肿瘤中,36.8%的胃癌和44.4%的结直肠癌为高msi。在7例患者中发现了种系致病性MMR变异。尽管有共同的超突变表型,但配对肿瘤之间重叠体细胞突变的比例一直很低(< 5%)。突变特征因MSI状态而异,包括SBS1/5(老化)和SBS15 (MMR缺乏)。值得注意的是,一名非lynch患者在两个肿瘤中都表现出MYC扩增,荧光原位杂交证实了这一点。结论:即使在具有共同种系易感性的患者中,发生在不同器官的原发性肿瘤也表现出实质性的基因组差异。这些发现表明,器官特异性选择压力驱动独立的肿瘤进化,强调了在多发性原发癌症病例中个体化分子分析和治疗靶向的必要性。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Intrapatient genomic divergence across multiple primary tumors in young Korean patients.

Intrapatient genomic divergence across multiple primary tumors in young Korean patients.

Intrapatient genomic divergence across multiple primary tumors in young Korean patients.

Intrapatient genomic divergence across multiple primary tumors in young Korean patients.

Purpose: Multiple primary tumors arising in the same individual pose challenges for precision oncology, particularly in the context of hereditary cancer syndromes such as Lynch syndrome. While these tumors may originate from a shared germline predisposition, it remains unclear whether they also share somatic alterations that could be therapeutically exploited. This study aimed to characterize the extent of somatic genomic overlap between synchronous or metachronous gastric and colorectal cancers within young Korean patients.

Methods: Nineteen patients diagnosed with both gastric and colorectal cancers before age 55 underwent whole exome sequencing of formalin-fixed paraffin-embedded tumor tissues. Microsatellite instability (MSI) status was determined, and germline mismatch repair (MMR) variants were assessed to identify Lynch syndrome cases. Somatic mutations, mutational signatures, and copy number alterations were analyzed to quantify intertumoral genomic similarity within individual patients.

Results: Among the 37 tumors analyzed, 36.8% of gastric and 44.4% of colorectal cancers were MSI-high. Germline pathogenic MMR variants were identified in seven patients. Despite shared hypermutated phenotypes, the proportion of overlapping somatic mutations between paired tumors was consistently low (< 5%). Mutational signatures varied by MSI status and included SBS1/5 (aging) and SBS15 (MMR deficiency). Notably, one non-Lynch patient exhibited MYC amplification in both tumors, confirmed by fluorescence in situ hybridization.

Conclusion: Even in patients with shared germline predisposition, primary tumors arising in different organs demonstrate substantial genomic divergence. These findings suggest that organ-specific selective pressures drive independent tumor evolution, underscoring the need for individualized molecular profiling and therapeutic targeting in cases of multiple primary cancers.

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