Detection of oncogenic mutations in paired circulating tumor DNA and circulating tumor cells in patients with hepatocellular carcinoma
| العنوان: | Detection of oncogenic mutations in paired circulating tumor DNA and circulating tumor cells in patients with hepatocellular carcinoma |
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| المؤلفون: | Patrick P.C. Boor, Maurice P.H.M. Jansen, Jaco Kraan, Dave Sprengers, Maikel P. Peppelenbosch, Jaap Kwekkeboom, Lisanne Noordam, Jean C. A. Helmijr, Zhouhong Ge |
| المساهمون: | Gastroenterology & Hepatology, Medical Oncology |
| المصدر: | Translational Oncology Translational Oncology, 14(7):101073. Neoplasia Press Translational Oncology, Vol 14, Iss 7, Pp 101073-(2021) |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Neuroblastoma RAS viral oncogene homolog, Cancer Research, NAFLD, non-alcoholic fatty liver disease, Hepatocellular carcinoma, NASH, non-alcoholic steatohepatitis, medicine.disease_cause, Macrovascular invasion, 03 medical and health sciences, 0302 clinical medicine, Circulating tumor cell, SDG 3 - Good Health and Well-being, medicine, VAF, variant allele frequency, Digital polymerase chain reaction, ctDNA, circulating tumor DNA, Liquid biopsy, Gene, RC254-282, Original Research, Mutation, Circulating tumor DNA, business.industry, Circulating tumor cells, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, medicine.disease, digestive system diseases, CTC, circulating tumor cells, TERT, telomerase reverse transcriptase, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, MVI, macrovascular invasion, Cancer research, ddPCR, droplet digital PCR, business, HCC, hepatocellular carcinoma, TERT promoter mutations |
| الوصف: | Highlights • In paired analysis CTCs were detected in 27% and ctDNA in 77% of HCC patients. • The TERT promoter mutation C228T was present in all patients with one or more ctDNA mutations, or detectable CTCs. • CtDNA (or TERT C228T) positivity was associated with macrovascular invasion and poor survival of advanced HCC patients. Background and aims Circulating tumor cells (CTCs) or circulating tumor DNA (ctDNA) may be used for diagnostic or prognostic purposes in patients with hepatocellular carcinoma (HCC). We aim to determine whether CTCs or ctDNA are suitable to determine oncogenic mutations in HCC patients. Methods Twenty-six mostly advanced HCC patients were enrolled. 30 mL peripheral blood from each patient was obtained. CellSearch system was used for CTC detection. A sequencing panel covering 14 cancer-relevant genes was used to identify oncogenic mutations. TERT promoter C228T and C250T mutations were determined by droplet digital PCR. Results CTCs were detected in 27% (7/26) of subjects but at low numbers (median: 2 cells, range: 1–15 cells) and ctDNA in 77% (20/26) of patients. Mutations in ctDNA were identified in several genes: TERT promoter C228T (77%, 20/26), TP53 (23%, 6/26), CTNNB1 (12%, 3/26), PIK3CA (12%, 3/26) and NRAS (4%, 1/26). The TERT C228T mutation was present in all patients with one or more ctDNA mutations, or detectable CTCs. The TERT C228T and TP53 mutations detected in ctDNA were present at higher levels in matched primary HCC tumor tissue. The maximal variant allele frequency (VAF) of ctDNA was linearly correlated with largest tumor size and AFP level (Log10). CtDNA (or TERT C228T) positivity was associated with macrovascular invasion, and positivity of ctDNA (or TERT C228T) or CTCs (≥ 2) correlated with poor patient survival. Conclusions Oncogenic mutations could be detected in ctDNA from advanced HCC patients. CtDNA analysis may serve as a promising liquid biopsy to identify druggable mutations. |
| تدمد: | 1936-5233 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::36783bf7b0ede0be0c84ee4674b68a5eTest https://pubmed.ncbi.nlm.nih.gov/33915518Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....36783bf7b0ede0be0c84ee4674b68a5e |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19365233 |
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