Plasma ctDNA enhances the tissue‑based detection of oncodriver mutations in colorectal cancer

• Wei Wang ^[1] ; Yisen Huang ^[2] ; Jianqiao Kong ^[3] ; Lin Lu ^[4] ; Qianxiu Liao ^[5] ; Jingtao Zhu ^[6] ; Tinghao Wang ^[6] ; Linghua Yan ^[7] ; Min Dai ^[8] ; Zhan Chen ^[9] ; Jun You ^[10]
  1. [1] The First People’s Hospital of Foshan, Foshan 528000, Guangdong, China
  2. [2] Department of Gastroenterology, Quanzhou First Hospital Affiliated to Fujian Medical University, Quanzhou 362002, Fujian, China
  3. [3] Department of General Surgery, Xiangyang No.1 People’s Hospital, Hubei University of Medicine, Xiangyang 441000, Hubei, China
  4. [4] Colorectal Surgery Department, General Hospital of Ningxia Medical University, Yinchuan 750001, Ningxia, China
  5. [5] Department of Laboratory Medicine, Chengdu First People’s Hospital, Chengdu 610041, Sichuan, China
  6. [6] The Third Clinical Medical College, Fujian Medical University, Xiamen 361001, Fujian, China
  7. [7] Shanghai Tongshu Biotechnology Co., Ltd, Shanghai 201900, China
  8. [8] Department of Pathology, Wuhu Hospital, East China Normal University (The Second People’s Hospital, Wuhu), Wuhu 241000, Anhui, China
  9. [9] Department of General Surgery, Chenggong Hospital of Xiamen University School of Medicine, Xiamen 361001, Fujian, China
  10. [10] Department of Gastrointestinal Oncology Surgery, Cancer Center, The First Affiliated Hospital of Xiamen University, School of Medicine, Xiamen University, Xiamen 361001, Fujian, China

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• Localización: Clinical & translational oncology, ISSN 1699-048X, Vol. 26, Nº. 8, 2024, págs. 1976-1987
• Idioma: inglés
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• Resumen

  • Purpose The advent of circulating tumor DNA (ctDNA) technology has provided a convenient and noninvasive means to continuously monitor cancer genomic data, facilitating personalized cancer treatment. This study aimed to evaluate the supplementary benefits of plasma ctDNA alongside traditional tissue-based next-generation sequencing (NGS) in identifying targetable mutations and tumor mutational burden (TMB) in colorectal cancers (CRC).

    Methods Our study involved 76 CRC patients, collecting both tissue and plasma samples for NGS. We assessed the concordance of gene mutational status between ctDNA and tissue, focusing on actionable genes such as KRAS, NRAS, PIK3CA, BRAF, and ERBB2. Logistic regression analysis was used to explore variables associated with discordance and positive mutation rates.

    Results In total, 26 cancer-related genes were identified. The most common variants in tumor tissues and plasma samples were in APC (57.9% vs 19.7%), TP53 (55.3% vs 22.4%) and KRAS (47.4% vs 43.4%). Tissue and ctDNA showed an overall concordance of 73.53% in detecting actionable gene mutations. Notably, plasma ctDNA improved detection for certain genes and gene pools. Variables significantly associated with discordance included gender and peritoneal metastases. TMB analysis revealed a higher detection rate in tissues compared to plasma, but combining both increased detection.

    Conclusions Our study highlights the importance of analyzing both tissue and plasma for detecting actionable mutations in CRC, with plasma ctDNA offering added value. Discordance is associated with gender and peritoneal metastases, and TMB analysis can benefit from a combination of tissue and plasma data. This approach provides valuable insights for personalized CRC treatment.