Identification and monitoring of mutations in circulating cell-free tumor DNA in hepatocellular carcinoma treated with lenvatinib
| Autor: | C. Nelson Hayes, Eisuke Murakami, Wataru Okamoto, Kenichiro Kodama, Takashi Nakahara, Masami Yamauchi, Kazuaki Chayama, Daiki Miki, Tomokazu Kawaoka, Masataka Tsuge, Yuji Teraoka, Hiroshi Aikata, Michio Imamura, Yasutoshi Fujii, Shinsuke Uchikawa, Atsushi Ono, Hatsue Fujino |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Oncology Male Cancer Research medicine.medical_specialty Carcinoma Hepatocellular ARID1A DNA Copy Number Variations Somatic cell Hepatocellular carcinoma Antineoplastic Agents medicine.disease_cause 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Medicine Humans Lenvatinib Copy-number variation Gene RC254-282 Aged Retrospective Studies Aged 80 and over Mutation Circulating tumor DNA business.industry Research Phenylurea Compounds Liver Neoplasms High-Throughput Nucleotide Sequencing Neoplasms. Tumors. Oncology. Including cancer and carcinogens Sequence Analysis DNA Middle Aged medicine.disease 030104 developmental biology chemistry Apoptosis 030220 oncology & carcinogenesis Quinolines Female business |
| Zdroj: | Journal of Experimental & Clinical Cancer Research, Vol 40, Iss 1, Pp 1-18 (2021) Journal of Experimental & Clinical Cancer Research : CR |
| ISSN: | 1756-9966 |
| Popis: | BackgroundThere has been a recent surge in interest in predicting biological effects associated with genomic alterations in order to implement personalized cancer treatment strategies. However, no reports have yet evaluated the utility of profiling blood-based circulating tumor DNA (ctDNA) in hepatocellular carcinoma (HCC) patients treated with lenvatinib (LEN).MethodWe retrospectively performed ctDNA next-generation sequencing (NGS) analysis in 24 patients with advanced HCC at baseline and 4 weeks after initiation of LEN. Association of the changes in variant allele frequencies (VAFs) during treatment and clinical outcome were evaluated.ResultsIn total, 131 single nucleotide variants, 17 indels, and 23 copy number variations were detected as somatic alterations in 28, 6, and 12 genes, respectively in 23 of 24 patients. The most frequently altered genes wereTP53(54%),CTNNB1(42%),TERT(42%),ATM(25%), andARID1A(13%). The reduction in the mean frequency of variants (VAFmean) following 4 weeks of LEN treatment was associated with longer progression-free survival. The specificity and sensitivity of the reduction of VAFmeanfor predicting partial response were 0.67 and 1.0, respectively, which were higher than those of serum α-fetoprotein level (0.10 and 0.93, respectively). No association between the mutation status at baseline and the effectiveness of LEN was observed.ConclusionOur study demonstrated that somatic alterations could be detected in the majority of advanced HCC patients by ctDNA profiling and that ctDNA-kinetics during LEN treatment was a useful marker of disease progression. These results suggest that ctDNA profiling is a promising method that provides valuable information in clinical practice. |
| Databáze: | OpenAIRE |
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