scholarly journals Clinical Significance of Telomerase Reverse-Transcriptase Promoter Mutations in Hepatocellular Carcinoma

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3771
Author(s):  
Francesca Pezzuto ◽  
Francesco Izzo ◽  
Pasquale De Luca ◽  
Elio Biffali ◽  
Luigi Buonaguro ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Sanger Sequencing ◽  
Tumour Size ◽  
Point Mutations ◽  
Inverse Correlation ◽  
Digital Pcr ◽  
Carbohydrate Antigen ◽  
Liver Cancers ◽  
Translational Start ◽  
Promoter Mutations

Telomerase reactivation during hepatocarcinogenesis is recurrently caused by two point mutations occurring most frequently at the nucleotide −124 (95%) and occasionally at the nucleotide −146 (<5%) upstream of the TERT translational start site in hepatocellular carcinoma (HCC). In this study, we designed a droplet digital PCR (ddPCR) assay to detect TERT promoter (TERTp) nucleotide change G>A at position −124 and to quantify the mutant allele frequency (MAF) in 121 primary liver cancers, including 114 HCC along with 23 autologous cirrhotic tissues, five cholangiocarcinoma (CC), and two hepato-cholangiocarcinoma (HCC-CC). All cases were evaluated for tumour markers such as α-fetoprotein (AFP), carbohydrate antigen 19-9 (CA19-9), and carcinoembryonic antigen (CEA). We compared the sensitivity of ddPCR and Sanger sequencing and investigated the prognostic relevance of TERTp mutations. The TERTp G>A transition was identified in 63.6% and 52.1% of HCC samples by ddPCR and Sanger sequencing, respectively. One out of 23 (4.3%) peri-tumour tissues tested positive only by ddPCR. One out of five CC (20%) and none of the HCC-CC were found concordantly mutated by the two methods. The TERTp MAF ranged from 2% to 66%, and the large majority (85.5%) of mutated samples showed a value above 20%. A statistically significant correlation was found between TERTp mutation and tumour size (p = 0.048), while an inverse correlation was observed with CA19-9 levels (p = 0.0105). Moreover, HCC patients with TERTp −124A had reduced survival. In conclusion, the single nucleotide variation G>A at position −124 in TERTp, detected either by ddPCR or by Sanger sequencing, showed a remarkable high frequency in HCC. Such mutation is associated with lower levels of CA19-9 and reduced survival in HCC patients suggesting that the TERTp status may represent a distinct signature of liver cancer subgroups.

scholarly journals Circulating tumor DNA is detectable in canine histiocytic sarcoma, oral malignant melanoma, and multicentric lymphoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anaïs Prouteau ◽  
Jérôme Alexandre Denis ◽  
Pauline De Fornel ◽  
Edouard Cadieu ◽  
Thomas Derrien ◽  
...  
Keyword(s):  
Residual Disease ◽  
Specific Antigen ◽  
Point Mutations ◽  
Antigen Receptor ◽  
Digital Pcr ◽  
Circulating Tumor Dna ◽  
Histiocytic Sarcoma ◽  
Oncology Research ◽  
Tumor Dna

AbstractCirculating tumor DNA (ctDNA) has become an attractive biomarker in human oncology, and its use may be informative in canine cancer. Thus, we used droplet digital PCR or PCR for antigen receptor rearrangement, to explore tumor-specific point mutations, copy number alterations, and chromosomal rearrangements in the plasma of cancer-affected dogs. We detected ctDNA in 21/23 (91.3%) of histiocytic sarcoma (HS), 2/8 (25%) of oral melanoma, and 12/13 (92.3%) of lymphoma cases. The utility of ctDNA in diagnosing HS was explored in 133 dogs, including 49 with HS, and the screening of recurrent PTPN11 mutations in plasma had a specificity of 98.8% and a sensitivity between 42.8 and 77% according to the clinical presentation of HS. Sensitivity was greater in visceral forms and especially related to pulmonary location. Follow-up of four dogs by targeting lymphoma-specific antigen receptor rearrangement in plasma showed that minimal residual disease detection was concordant with clinical evaluation and treatment response. Thus, our study shows that ctDNA is detectable in the plasma of cancer-affected dogs and is a promising biomarker for diagnosis and clinical follow-up. ctDNA detection appears to be useful in comparative oncology research due to growing interest in the study of natural canine tumors and exploration of new therapies.

Virtual Fluorescence Color Channels by Selective Photobleaching in Digital PCR Applied to the Quantification of KRAS Point Mutations

2021 ◽  
Author(s):  
Franziska Schlenker ◽  
Elena Kipf ◽  
Nadine Borst ◽  
Tobias Hutzenlaub ◽  
Roland Zengerle ◽  
...  
Keyword(s):  
Point Mutations ◽  
Digital Pcr ◽  
Fluorescence Color ◽  
Color Channels

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 Hepatic Epithelioid Hemangioendothelioma Presenting Synchronously with Hepatocellular Carcinoma

2021 ◽  
pp. 344-351
Author(s):  
Hiroki Kanno ◽  
Toshihiro Sato ◽  
Ryuta Midorikawa ◽  
Satoki Kojima ◽  
Shogo Fukutomi ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Carbohydrate Antigen ◽  
Epithelioid Hemangioendothelioma ◽  
Arterial Phase ◽  
Rapid Progression ◽  
Imaging Findings ◽  
Liver Segment ◽  
Contrast Enhanced ◽  
Well Differentiated ◽  
Enhanced Computed Tomography

Hepatic epithelioid hemangioendothelioma (EHE) is a rare malignant tumor with unknown pathogenesis. Herein, we report a case of a hepatic EHE presenting synchronously with a hepatocellular carcinoma (HCC). To the best of our knowledge, this is the second case report of synchronous hepatic EHE and HCC. An 84-year-old man presented with back pain. During examination, a tumor in liver segment 3 was coincidentally detected. Tumor marker (carbohydrate antigen 19-9, alpha-fetoprotein, and protein induced by vitamin K absence or antagonist-II) levels were elevated. Contrast-enhanced computed tomography revealed perinodular enhancement in the arterial and portal phases. Another tumor was detected in liver segment 2, which was homogeneously enhanced in the arterial phase, followed by washout in the portal and late phases. Based on these imaging findings, we diagnosed the tumor in segment 3 as a solitary cholangiocellular carcinoma and the tumor in segment 2 as a solitary HCC. Lateral sectionectomy of the liver was performed. Microscopically, spindle-shaped and epithelioid cells were present in the tumor in segment 3. On immunohistochemistry, the tumor cells were positive for CD31 and CD34, focally positive for D2-40, and negative for AE1/AE3. Therefore, the tumor in segment 3 was ultimately diagnosed as an EHE and the tumor in segment 2 as a well-differentiated HCC. Preoperative diagnosis of EHE is difficult owing to the lack of specific findings. Intratumoral calcification, halo sign, and lollipop sign are occasionally found in EHE and are useful imaging findings for diagnosis. Clinical behavior is unpredictable, ranging from indolent growth to rapid progression. Clinical or pathological predictors of the course of EHE are urgently required.

scholarly journals Current Trends and Characteristics of Hepatocellular Carcinoma in Patients with Autoimmune Liver Diseases

Cancers ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1023
Author(s):  
Eirini I. Rigopoulou ◽  
George N. Dalekos
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Liver Diseases ◽  
Treatment Modalities ◽  
Primary Biliary Cholangitis ◽  
Autoimmune Liver Diseases ◽  
Increased Risk ◽  
Liver Cancers ◽  
Medium Risk ◽  
Causes Of Mortality

Hepatocellular carcinoma (HCC), the commonest among liver cancers, is one of the leading causes of mortality among malignancies worldwide. Several reports demonstrate autoimmune liver diseases (AILDs), including autoimmune hepatitis (AIH), primary biliary cholangitis (PBC), and primary sclerosing cholangitis (PSC) to confer increased risk of hepatobiliary malignancies, albeit at lower frequencies compared to other liver diseases. Several parameters have been recognized as risk factors for HCC development in AIH and PBC, including demographics such as older age and male sex, clinical features, the most decisive being cirrhosis and other co-existing factors, such as alcohol consumption. Moreover, biochemical activity and treatment response have been increasingly recognized as prognostic factors for HCC development in AIH and PBC. As available treatment modalities are effective only when HCC diagnosis is established early, surveillance has been proven essential for HCC prognosis. Considering that the risk for HCC is not uniform between and within disease groups, refinement of screening strategies according to prevailing demographic, clinical, and molecular risk factors is mandated in AILDs patients, as personalized HCC risk prediction will offer significant advantage in patients at high and/or medium risk. Furthermore, future investigations should draw attention to whether modification of immunosuppression could benefit AIH patients after HCC diagnosis.

scholarly journals TERT promoter mutations in thyroid cancer: a report from a Middle Eastern population

2015 ◽  
Vol 22 (6) ◽  
pp. 901-908 ◽  
Author(s):  
Ebtesam Qasem ◽  
Avaniyapuram Kannan Murugan ◽  
Hindi Al-Hindi ◽  
Mingzhao Xing ◽  
Mai Almohanna ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Middle East ◽  
Direct Sequencing ◽  
Tumour Size ◽  
Middle Eastern ◽  
Middle Eastern Population ◽  
Thyroid Adenomas ◽  
Cell Variant ◽  
Hürthle Cell Thyroid Cancer ◽  
Promoter Mutations

Telomerase reverse transcriptase (TERT) promoter mutations C228T and C250T have recently been described in follicular cell-derived thyroid cancer (TC) in patients from North America and Europe. In this study, we explored whether these findings could be replicated in patients from a different ethnic group. We screened 17 benign thyroid adenomas and 265 TC samples from patients in the Middle East for these mutations by PCR and direct sequencing using DNA isolated from paraffin-embedded tumor tissues. None of the 17 benign adenomas harbored TERT promoter mutations. Of 265 TC, 34 (12.8%) harbored TERT promoter mutations, including 10/153 (6.5%) conventional papillary TC (CPTC), 8/57 (14.0%) follicular variant PTC, 9/30 (30%) tall cell variant PTC, 1/3 (30%) Hurthle cell thyroid cancer (HTC), 1/5 (20%) follicular TC, and 5/13 (38.5%) poorly differentiated TC. C250T mutation was present in only 6/265 (2.3%) cases, while C228T mutation was present in a total of 28/265 (10.6%) cases. These two mutations were mutually exclusive. TERT promoter mutations were significantly more common in older (≥45 years) than younger patients and were associated with larger tumour size, vascular invasion, higher TNM stage (stage III and IV), BRAFV600E mutation and persistent/recurrent disease at 6–12 months after initial treatment and at the last follow up. These associations were stronger in non-CPTC. Thus, this study on a large cohort of TC patients from Middle East demonstrates that TERT promoter mutations are relatively common, especially in the non-CPTC, and are associated with more aggressive histopathological features, BRAFV600E mutation, and disease persistence/recurrence than the WT TERT.

scholarly journals Inflammatory indexes in preoperative blood routine to predict early recurrence of hepatocellular carcinoma after curative hepatectomy

BMC Surgery ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
YiFeng Wu ◽  
ChaoYong Tu ◽  
ChuXiao Shao
Keyword(s):  
Risk Factors ◽  
Hepatocellular Carcinoma ◽  
Tumour Size ◽  
Area Under The Curve ◽  
Early Recurrence ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Lymphocyte Ratio ◽  
Inflammatory Index ◽  
Curative Hepatectomy

Abstract Background The inflammation indexes in blood routine play an essential role in evaluating the prognosis of patients with hepatocellular carcinoma, but the effect on early recurrence has not been clarified. The study aimed to investigate the risk factors of early recurrence (within 2 years) and recurrence-free survival after curative hepatectomy and explore the role of inflammatory indexes in predicting early recurrence. Methods The baseline data of 161 patients with hepatocellular carcinoma were analyzed retrospectively. The optimal cut-off value of the inflammatory index was determined according to the Youden index. Its predictive performance was compared by the area under the receiver operating characteristic curve. Logistic and Cox regression analyses were used to determine the risk factors of early recurrence and recurrence-free survival. Results The area under the curve of monocyte to lymphocyte ratio (MLR) for predicting early recurrence was 0.700, which was better than systemic inflammatory response index (SIRI), neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR) and systemic immune-inflammatory index (SII). MLR, tumour size, tumour differentiation and BCLC stage are all risk factors for early recurrence and recurrence-free survival of HCC. Combining the above four risk factors to construct a joint index, the area under the curve for predicting early recurrence was 0.829, which was better than single MLR, tumour size, tumour differentiation and BCLC stage. Furthermore, with the increase of risk factors, the recurrence-free survival of patients is worse. Conclusion The combination of MLR and clinical risk factors is helpful for clinicians to identify high-risk patients with early recurrence and carry out active postoperative adjuvant therapy to improve the prognosis of patients.

scholarly journals Radiofrequency Ablation of Hepatocellular Carcinoma: A Literature Review

2011 ◽  
Vol 2011 ◽  
pp. 1-9 ◽  
Author(s):  
Yasunori Minami ◽  
Masatoshi Kudo
Keyword(s):  
Hepatocellular Carcinoma ◽  
Radiofrequency Ablation ◽  
Safety Margin ◽  
Surgical Techniques ◽  
Evidence Base ◽  
Current Status ◽  
Probe Design ◽  
Curative Therapy ◽  
Management Of Complications ◽  
Liver Cancers

Radiofrequency ablation (RFA) of liver cancers can be performed safely using percutaneous, laparoscopic, or open surgical techniques, and much of the impetus for the use of RFA has come from cohort series that have provided an evidence base for this technique. Here, we give an overview of the current status of radiofrequency ablation (RFA) for hepatocellular carcinoma (HCC), including its physical properties, to assess the characteristics that make this technique applicable in clinical practice. We review the technical development of probe design and summarize current indications and outcomes of reported clinical use. An accurate evaluation of treatment response is very important to secure successful RFA therapy since a sufficient safety margin (at least 0.5 cm) can prevent local tumor recurrences. We also provide a profile of side effects and information on the integration of this technique into the general management of patients with HCC. To minimize complications of RFA, physicians should be familiar with each feature of complication. Appropriate management of complications is essential for successful RFA treatment. Moreover, adjuvant therapy, such as molecular targeted therapies following curative therapy, is expected to further improve survival after RFA.

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