Circulating tumor DNA in patients with colorectal adenomas: assessment of detectability and genetic heterogeneity

被引:0
|
作者
Ni Ni Moe Myint
Ajay M. Verma
Daniel Fernandez-Garcia
Panchali Sarmah
Patrick S. Tarpey
Saif Sattar Al-Aqbi
Hong Cai
Ricky Trigg
Kevin West
Lynne M. Howells
Anne Thomas
Karen Brown
David S. Guttery
Baljit Singh
Howard J. Pringle
Ultan McDermott
Jacqui A. Shaw
Alessandro Rufini
机构
[1] University of Leicester,Leicester Cancer Research Centre
[2] University Hospital of Leicester,University of Leicester
[3] Wellcome Sanger Institute,Department of Pathology and Poultry Diseases, Faculty of Veterinary Medicine
[4] University of Kufa,undefined
[5] Kettering General Hospital NHS Foundation Trust,undefined
来源
Cell Death & Disease | / 9卷
关键词
D O I
暂无
中图分类号
学科分类号
摘要
Improving early detection of colorectal cancer (CRC) is a key public health priority as adenomas and stage I cancer can be treated with minimally invasive procedures. Population screening strategies based on detection of occult blood in the feces have contributed to enhance detection rates of localized disease, but new approaches based on genetic analyses able to increase specificity and sensitivity could provide additional advantages compared to current screening methodologies. Recently, circulating cell-free DNA (cfDNA) has received much attention as a cancer biomarker for its ability to monitor the progression of advanced disease, predict tumor recurrence and reflect the complex genetic heterogeneity of cancers. Here, we tested whether analysis of cfDNA is a viable tool to enhance detection of colon adenomas. To address this, we assessed a cohort of patients with adenomas and healthy controls using droplet digital PCR (ddPCR) and mutation-specific assays targeted to trunk mutations. Additionally, we performed multiregional, targeted next-generation sequencing (NGS) of adenomas and unmasked extensive heterogeneity, affecting known drivers such as APC, KRAS and mismatch repair (MMR) genes. However, tumor-related mutations were undetectable in patients’ plasma. Finally, we employed a preclinical mouse model of Apc-driven intestinal adenomas and confirmed the inability to identify tumor-related alterations via cfDNA, despite the enhanced disease burden displayed by this experimental cancer model. Therefore, we conclude that benign colon lesions display extensive genetic heterogeneity, that they are not prone to release DNA into the circulation and are unlikely to be reliably detected with liquid biopsies, at least with the current technologies.
引用
收藏
相关论文
共 50 条
  • [21] Circulating free tumor DNA and colorectal cancer
    Lecomte, T.
    Ceze, N.
    Dorval, E.
    Laurent-Puig, P.
    GASTROENTEROLOGIE CLINIQUE ET BIOLOGIQUE, 2010, 34 (12): : 662 - 681
  • [23] Circulating tumor (ct) DNA captures intrapatient heterogeneity in metastatic colorectal (mCRC) patients (pts) progressing to FOLFIRI plus panitumumab
    Vidal, J.
    Vieitez, J. M.
    Paez, D.
    Santos, C.
    Falco, E.
    Lopez Lopez, C.
    Valladares-Ayerbes, M.
    Robles, L.
    Garcia-Alfonso, P.
    Duran Ogaya, G.
    Azuara, D.
    Dalmeses, A.
    Bellosillo Paricio, B.
    Capella, G.
    Salazar, R.
    Aranda Aguilar, E.
    Montagut, C.
    ANNALS OF ONCOLOGY, 2017, 28
  • [24] Circulating tumor cells Exploring intratumor heterogeneity of colorectal cancer
    Raimondi, Cristina
    Nicolazzo, Chiara
    Gradilone, Angela
    Giannini, Giuseppe
    De Falco, Elena
    Chimenti, Isotta
    Varriale, Elisa
    Hauch, Siegfried
    Plappert, Linda
    Cortesi, Enrico
    Gazzaniga, Paola
    CANCER BIOLOGY & THERAPY, 2014, 15 (05) : 496 - 503
  • [25] Genetic Heterogeneity of Single Circulating Tumour Cells in Colorectal Carcinoma
    Bin Hamid, Faysal
    Gopalan, Vinod
    Matos, Marco
    Lu, Cu-Tai
    Lam, Alfred King-yin
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2020, 21 (20) : 1 - 14
  • [26] Genetic profiling of circulating tumor cells in patients with advanced colorectal cancer.
    Ernst, D.
    Kubisch, I.
    de Albuquerque, A.
    Kaul, S.
    Boese-Landgraf, J.
    Fersis, N.
    JOURNAL OF CLINICAL ONCOLOGY, 2010, 28 (15)
  • [27] Clinical relevance of tumor fraction assessment from circulating tumor DNA in metastatic colorectal cancer.
    Morris II, Van K.
    Quintanilha, Julia
    Elvin, Julia A.
    Graf, Ryon P.
    Kopetz, Scott
    JOURNAL OF CLINICAL ONCOLOGY, 2025, 43 (4_SUPPL) : 237 - 237
  • [28] Exosomal DNA has the potential to detect tumor heterogeneity in patients with colorectal cancer
    Kuriyama, Sho
    Yamada, Takeshi
    Matsuda, Akihisa
    Shinji, Seiichi
    Sonoda, Hiromichi
    Ohta, Ryo
    Yonaga, Kazuhide
    Iwai, Takuma
    Takeda, Kohki
    Ueda, Koji
    Miyasaka, Toshimitsu
    Yoshida, Hiroshi
    CANCER SCIENCE, 2022, 113
  • [29] Circulating tumor DNA-guided minimal residual disease assessment in colorectal cancer
    Chakrabarti, Sakti
    Mahipal, Amit
    PHARMACOGENOMICS, 2023,
  • [30] Utility of circulating tumor DNA in patients undergoing hepatectomy for colorectal liver metastases
    Cnockaert, Philippine
    Muscari, Fabrice
    Maulat, Charlotte
    HEPATOBILIARY SURGERY AND NUTRITION, 2023, 12 (05) : 736 - 739