scholarly journals Prediction of the prognosis of advanced hepatocellular carcinoma by TERT promoter mutations in circulating tumor DNA

2020 ◽  
Author(s):  
Mami Hirai ◽  
Hideaki Kinugasa ◽  
Kazuhiro Nouso ◽  
Shumpei Yamamoto ◽  
Hiroyuki Terasawa ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Circulating Tumor Dna ◽  
Advanced Hepatocellular Carcinoma ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations ◽  
Tumor Dna

scholarly journals Combining tissue and circulating tumor DNA increases the detection rate of a CTNNB1 mutation in hepatocellular carcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Stine Karlsen Oversoe ◽  
Michelle Simone Clement ◽  
Britta Weber ◽  
Henning Grønbæk ◽  
Stephen Jacques Hamilton-Dutoit ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mutation Rate ◽  
Detection Rate ◽  
Tumor Tissue ◽  
Circulating Tumor Dna ◽  
Treatment Modalities ◽  
Advanced Hepatocellular Carcinoma ◽  
Tissue Samples ◽  
The Impact ◽  
Tumor Dna

Abstract Background and aims Studies suggest that mutations in the CTNNB1 gene are predictive of response to immunotherapy, an emerging therapy for advanced hepatocellular carcinoma (HCC). Analysis of circulating tumor DNA (ctDNA) offers the possibility of serial non-invasive mutational profiling of tumors. Combining tumor tissue and ctDNA analysis may increase the detection rate of mutations. This study aimed to evaluate the frequency of the CTNNB1 p.T41A mutation in ctDNA and tumor samples from HCC patients and to evaluate the concordance rates between plasma and tissue. We further evaluated changes in ctDNA after various HCC treatment modalities and the impact of the CTNNB1 p.T41A mutation on the clinical course of HCC. Methods We used droplet digital PCR to analyze plasma from 95 patients and the corresponding tumor samples from 37 patients during 3 years follow up. Results In tumor tissue samples, the mutation rate was 8.1% (3/37). In ctDNA from HCC patients, the CTNNB1 mutation rate was 9.5% (9/95) in the pre-treatment samples. Adding results from plasma analysis to the subgroup of patients with available tissue samples, the mutation detection rate increased to 13.5% (5/37). There was no difference in overall survival according to CTNNB1 mutational status. Serial testing of ctDNA suggested a possible clonal evolution of HCC or arising multicentric tumors with separate genetic profiles in individual patients. Conclusion Combining analysis of ctDNA and tumor tissue increased the detection rate of CTNNB1 mutation in HCC patients. A liquid biopsy approach may be useful in a tailored therapy of HCC.

scholarly journals Significance of TERT Genetic Alterations and Telomere Length in Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (9) ◽  
pp. 2160
Author(s):  
Jeong-Won Jang ◽  
Jin-Seoub Kim ◽  
Hye-Seon Kim ◽  
Kwon-Yong Tak ◽  
Soon-Kyu Lee ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Telomere Length ◽  
Differentially Expressed Gene ◽  
Genetic Alterations ◽  
Tissue Samples ◽  
Protein Protein Interaction ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations ◽  
Tert Expression

Telomerase reverse transcriptase (TERT) mutations are reportedly the most frequent somatic genetic alterations in hepatocellular carcinoma (HCC). An integrative analysis of TERT-telomere signaling during hepatocarcinogenesis is lacking. This study aimed to investigate the clinicopathological association and prognostic value of TERT gene alterations and telomere length in HCC patients undergoing hepatectomy as well as transarterial chemotherapy (TACE). TERT promoter mutation, expression, and telomere length were analyzed by Sanger sequencing and real-time PCR in 305 tissue samples. Protein–protein interaction (PPI) analysis was performed to identify a set of genes that physically interact with TERT. The PPI analysis identified eight key TERT-interacting genes, namely CCT5, TUBA1B, mTOR, RPS6KB1, AKT1, WHAZ, YWHAQ, and TERT. Among these, TERT was the most strongly differentially expressed gene. TERT promoter mutations were more frequent, TERT expression was significantly higher, and telomere length was longer in tumors versus non-tumors. TERT promoter mutations were most frequent in HCV-related HCCs and less frequent in HBV-related HCCs. TERT promoter mutations were associated with higher TERT levels and longer telomere length and were an independent predictor of worse overall survival after hepatectomy. TERT expression was positively correlated with tumor differentiation and stage progression, and independently predicted shorter time to progression after TACE. The TERT-telomere network may have a crucial role in the development and progression of HCC. TERT-telomere abnormalities might serve as useful biomarkers for HCC, but the prognostic values may differ with tumor characteristics and treatment.

scholarly journals Clinical significance of combined circulating TERT promoter mutations and miR-122 expression for screening HBV-related hepatocellular carcinoma

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Ngo Tat Trung ◽  
Nghiem Xuan Hoan ◽  
Pham Quang Trung ◽  
Mai Thanh Binh ◽  
Hoang Van Tong ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Clinical Significance ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

Mutations in circulating tumor DNA predict primary resistance to systemic therapies in patients with advanced hepatocellular carcinoma

2020 ◽  
Vol 73 ◽  
pp. S900
Author(s):  
Johann von Felden ◽  
Amanda J. Craig ◽  
Ismail Labgaa ◽  
Teresa Garcia-Lezana ◽  
Delia D’Avola ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Circulating Tumor Dna ◽  
Advanced Hepatocellular Carcinoma ◽  
Primary Resistance ◽  
Tumor Dna ◽  
Systemic Therapies

scholarly journals Limited Clinical and Diagnostic Utility of Circulating Tumor DNA Detection in Patients with Early-Stage Well-Differentiated Thyroid Cancer: Comparison with Benign Thyroid Nodules and Healthy Individuals

Healthcare ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 386
Author(s):  
Yong Joon Suh ◽  
Mi Jung Kwon ◽  
Hye-Mi Noh ◽  
Hong Kyu Lee ◽  
Yong Joon Ra ◽  
...  
Keyword(s):  
Kras Mutation ◽  
Early Stage ◽  
Circulating Tumor Dna ◽  
Diagnostic Utility ◽  
Plasma Samples ◽  
Healthy Individuals ◽  
Thyroid Cancers ◽  
Tert Promoter ◽  
Tert Promoter Mutations ◽  
Promoter Mutations

Limited data are available on the diagnostic utility of circulating tumor DNA (ctDNA) in early-stage thyroid cancers for BRAF, KRAS, NRAS, and TERT promoter mutations, which are known detectable markers for thyroid cancers. Here, we analyzed the above driver mutations in ctDNA and matched neoplastic tissues from patients with early-stage thyroid cancers in order to investigate diagnostic utility of circulating markers in distinguishing from other mimicking thyroid lesions and healthy individuals. In total, 73 matched neoplastic tissue and plasma samples [thyroid cancers (n = 62), benign thyroid disorders (n = 8), and parathyroid lesions (n = 3)] and 54 plasma samples from healthy individuals (as controls) were analyzed for BRAF, KRAS, NRAS, and TERT promoter mutations using peptide nucleic acid clamp real-time PCR. Although only one patient with an indeterminate lesion on thyroid cytology showed KRAS mutation (codon 146) in the preoperative plasma, that KRAS mutation was not identified in the stage I papillary thyroid carcinoma tissue. In the remaining 72 plasma samples, no other mutations were identified in BRAF, NRAS, and TERT promoter genes. The concordance rates of mutational results between the plasma and tumor tissue or metastatic lymph node were very low. One (1.9%) of the 54 healthy individuals harbored a KRAS mutation in the plasma samples. The ctDNA results did not represent the mutational profile of primary or metastatic thyroid cancers, warranting a caution for interpretation. The clinical utility of BRAF, KRAS, NRAS, and TERT promoter mutation analysis on ctDNA appears to be limited to early-stage thyroid cancers.

scholarly journals Combining Tissue and Circulating Tumor DNA Increases the Detection Rate of CTNNB1 Mutation in Hepatocellular Carcinoma

2020 ◽  
Author(s):  
Stine Karlsen Oversoe ◽  
Michelle Simone Clement ◽  
Britta Weber ◽  
Henning Grønbæk ◽  
Stephen Jacques Hamilton-Dutoit ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Mutation Rate ◽  
Detection Rate ◽  
Tumor Tissue ◽  
Circulating Tumor Dna ◽  
Treatment Modalities ◽  
Advanced Hepatocellular Carcinoma ◽  
Tissue Samples ◽  
The Impact ◽  
Tumor Dna

Abstract Background and aims: Studies suggest that mutations in the CTNNB1 gene are predictive of response to immunotherapy, an emerging therapy for advanced hepatocellular carcinoma (HCC). Analysis of circulating tumor DNA (ctDNA) offers the possibility of serial non-invasive mutational profiling of tumors. Combining tumor tissue and ctDNA analysis may increase the detection rate of mutations.This study aimed to evaluate the frequency of the CTNNB1 p.T41A mutation in ctDNA and tumor samples from HCC patients and to evaluate the concordance rates between plasma and tissue. We further evaluated changes in ctDNA after various HCC treatment modalities and the impact of the CTNNB1 p.T41A mutation on the clinical course of HCC.Methods: We used droplet digital PCR to analyze plasma from 95 patients and the corresponding tumor samples from 37 patients during three years of follow up. Results: In tumor tissue samples, the mutation rate was 8.1% (3/37). In ctDNA from HCC patients, we found a CTNNB1 mutation rate of 9.5% (9/95) in the pre-treatment samples. Adding results from plasma analysis to the subgroup of patients with available tissue samples, the mutation detection rate increased to 13.5% (5/37). There was no difference in overall survival according to CTNNB1 mutational status. Serial testing of ctDNA indicated a clonal evolution of HCC or arising of multicentric tumors with separate genetic profiles.Conclusion: Combining analysis of ctDNA and tumor tissue increased the detection rate of CTNNB1 mutation in HCC patients. A liquid biopsy approach may be useful in a tailored therapy of HCC.

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