Genomic alterations linked to recurrence risk in high-grade serous ovarian cancer revealed by deep targeted sequencing

通过深度靶向测序揭示与高级别浆液性卵巢癌复发风险相关的基因组改变

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Abstract

High-grade serous ovarian cancer (HGSOC) is a highly fatal disease with frequent recurrence and high mortality rates, despite ongoing treatment advancements. Next-generation sequencing (NGS) is an experimental technique used to obtain extensive genetic information, making it a key component of precision medicine. We conducted a study based on a sample of 108 patients with HGSOC retrospectively selected from Severance Hospital and Gangnam Severance Hospital. We aimed to identify the genetic alterations associated with HGSOC recurrence and survival using deep targeted sequencing. Somatic mutations in NF1, FAT1, ROS1, NOTCH3, and BLM are more common in recurrent ovarian cancer. Differences in copy number variations (CNVs) and gene fusion events were also observed. Using multivariable stepwise logistic regression, we found that the presence of exonic mutations in the NF1 and ROS1 genes and a tumor mutational burden (TMB) value ≥ 10 were significantly associated with recurrence in HGSOC patients. High TMB (TMB ≥ 10), Del 13q14.3 mutation, and exonic mutations in NOTCH3, NF1, ROS1, ATM, FAT1, and SLX4 genes were associated with recurrence-free survival (RFS), while the ARID1A gene was observed to be associated with overall survival. This study identified key genetic alterations associated with recurrence and survival in HGSOC and confirmed that specific genetic mutations were linked to disease prognosis. We expect that these findings will contribute to more precise prognosis prediction and the development of personalized therapeutic strategies for patients with recurrent ovarian cancer. SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1038/s41598-025-26481-4.

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