Kim Young-Gon, Lee Boram, Ha Changhee, Lee Cheonghwa, Jung Hyun Ae, Sun Jong-Mu, Lee Se-Hoon, Ahn Myung-Ju, Choi Yoon-La, Park Sehhoon, Kim Jong-Won
Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Front Oncol. 2024 Oct 24;14:1463341. doi: 10.3389/fonc.2024.1463341. eCollection 2024.
Numerous studies have suggested high concordance between tissue and circulating tumor DNA (ctDNA) comprehensive genomic profiling (CGP) tests but only few of them focused on fusions. In addition, atypical breakpoints occasionally detected from DNA-based fusion detection make interpretation difficult, and their clinical significance remains unclear. This study evaluated the clinical utility of ctDNA CGP for fusion detection.
The results of ctDNA CGP tests performed on patients with stage IV non-small cell lung cancer during routine clinical care were retrospectively reviewed. The concordance between ctDNA CGP and combined tissue test results was analyzed using CGP, immunohistochemistry, fluorescence hybridization, and reverse transcription polymerase chain reaction. The clinical significance of fusions detected by ctDNA CGP, including those with atypical breakpoints at the DNA level, was assessed.
In total, 264 patients were tested with ctDNA CGP. Fusions were detected in 27 patients (10.2%), and the fusion drivers were (n=12, 4.6%), (n=9, 3.4%), (n=4, 1.5%), and (n=2, 0.8%). The overall prevalence of fusion in tissue CGP was comparable to that in ctDNA CGP. A total of 371 ctDNA-tissue test pairs were available, and the overall positive and negative percent agreement rates were 92.9% (13/14) and 100.0% (357/357), respectively. One IHC-positive and ctDNA CGP-negative case did not respond to -targeted therapy. Response to targeted therapy was assessed in 16 patients, and a partial response was achieved in all patients, including four with atypical breakpoints.
Fusion detection using ctDNA CGP showed high concordance with tissue tests and accuracy in predicting therapeutic responses in patients with non-small cell lung cancer. ctDNA CGP may provide an important diagnostic tool for fusion detection.
众多研究表明组织与循环肿瘤DNA（ctDNA）综合基因组分析（CGP）检测之间具有高度一致性，但其中仅有少数研究聚焦于融合基因。此外，基于DNA的融合基因检测偶尔会检测到非典型断点，这使得解读变得困难，其临床意义仍不明确。本研究评估了ctDNA CGP用于融合基因检测的临床效用。
回顾性分析了在常规临床护理期间对IV期非小细胞肺癌患者进行的ctDNA CGP检测结果。使用CGP、免疫组织化学、荧光杂交和逆转录聚合酶链反应分析ctDNA CGP与联合组织检测结果之间的一致性。评估了ctDNA CGP检测到的融合基因的临床意义，包括那些在DNA水平具有非典型断点的融合基因。
共有264例患者接受了ctDNA CGP检测。27例患者（10.2%）检测到融合基因，融合基因驱动因子包括（n = 12，4.6%）、（n = 9，3.4%）、（n = 4，1.5%）和（n = 2，0.8%）。组织CGP中融合基因的总体患病率与ctDNA CGP中的相当。共有371对ctDNA-组织检测结果，总体阳性和阴性百分比一致率分别为92.9%（13/14）和100.0%（357/357）。1例免疫组化阳性而ctDNA CGP阴性的病例对靶向治疗无反应。对16例患者评估了靶向治疗反应，所有患者均获得部分缓解，包括4例具有非典型断点的患者。
使用ctDNA CGP进行融合基因检测与组织检测具有高度一致性，并且在预测非小细胞肺癌患者的治疗反应方面具有准确性。ctDNA CGP可能为融合基因检测提供一种重要的诊断工具。
