Use of Liquid Biopsy to Identify Actionable Mutations in Patients with Recurrent or Advanced Colorectal Cancer in Clinical Practice: A Single Institution Experience

臨床使用液態切片檢測找尋復發或晚期大腸直腸癌患者具臨床治療參考意義基因突變－單一機構經驗

林華卿(Hua-Ching Lin) ； 陳國維(Kuo-Wei Chen)

《中華民國大腸直腸外科醫學會雜誌》 33卷2期 (2022/06) Pp. 67-75

https://doi.org/10.6312/SCRSTW.202206_33(2).11105

摘要

Purpose. Patients with recurrent or late stage colorectal cancer (CRC) could develop multiple lesions. Tissue biopsy is not always ideal for genetic testing because the tissue can be scarce and difficult to access. We conducted a retrospective study of circulating tumor DNA(ctDNA) next-generation sequencing analysis in patients with recurrent or advanced CRC. The purpose of the study was to explore the utility of ctDNA tests in providing clinical actionable information in colorectal cancer. Methods. Twenty patients, ten men and ten women, were included. Each patient's peripheral blood was collected and centrifuged to extract both plasma cell-free DNA and buffy coat white blood cell (WBC) DNA. Both plasma cfDNA and WBC gDNA were sequenced using hybrid capture - based NGS panel (74 genes). The sequencing results were then compared and analyzed to report ctDNA mutation by filtering out the false positive variants that could be produced by clonal hematopoiesis. Results. TP53 was the most frequently mutated gene (15/20) in these patients. Among the patients, thirteen had concordant KRAS hotspots or BRAF V600E status compared with the original tissue pathology results at diagnosis. Sixteen patients (16/20) had detectable mutations which could lead to next therapy option or treatment efficacy monitoring purpose. Conclusion. Simple blood ctDNA tests could reflect the tumor genome profile and provide clinicians with an alternative means of exploring the next possible regimen or evaluating the treatment efficacy.

關鍵字

CRC ； ctDNA ； NGS ； Clonal hematopoiesis

並列摘要

目的：復發或第四期的大腸直腸癌患者常具有多處腫瘤轉移，而此時若需要進行組織採檢以進行基因檢測可能會受限於患者組織取得不易或可取得的組織稀少以致無法進行。我們以回顧性的方式分析了二十位大腸直腸癌患者的循環腫瘤DNA次世代定序檢測結果。本研究的目的是探討循環腫瘤DNA檢測對於提供有大腸癌治療有意義臨床資訊的臨床應用性。方法：分析包含二十位患者。每位患者皆抽血並離心，分別萃取上層血漿的游離懸浮DNA以及白血球細胞核內的DNA，接著使用雜交體捕捉技術平台各自同時定序74個臨床癌症標靶治療相關基因。最後，兩邊DNA定序結果同時進行比對分析以去除來自克隆性造血所造成的非腫瘤相關基因突變的干擾。結果：TP53基因突變出現在十五位患者中（15/20）。所有二十位患者中，十三位的KRAS熱點基因突變與BRAF V600E基因突變狀態與確診時的標準臨床組織檢測一致。十六位患者於檢測中找到可能作為下一線的治療選擇或作為後續評估治療效果的基因突變。結論：簡單的抽血檢測循環腫瘤DNA可以顯示患者目前體內腫瘤的基因變異狀態並提供臨床醫師另一個檢測工具來找尋可能的治療標的或是評估現行治療的效果。

並列關鍵字

大腸直腸癌 ； 循環腫瘤DNA ； 次世代定序 ； 克隆性造血

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