Clinicopathologic and genomic characteristics of biliary tract carcinomas with TERT promoter mutations among East Asian population.

Pathol Res Pract

Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea; Center for Companion Diagnostics, Precision Medicine Research Institute, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address:

Published: December 2024

Telomerase reverse transcriptase gene promoter (TERT) mutations are biomarkers that predict survival and responses to immune checkpoint inhibitors in various malignancies. However, their prevalence and clinicopathologic characteristics in biliary tract carcinomas are largely unknown. We performed a comprehensive genomic profiling of formalin-fixed paraffin-embedded tumor tissue from 485 carcinomas, including intrahepatic (n = 220), perihilar (n = 54), distal biliary tract (n = 110), and gallbladder (n = 101) cancers, using next-generation sequencing. TERT mutations were observed in 50 out of 485 biliary tract cancers (10.3 %) consisting of 39 C228T (78.0 %) and 11 C250T (22.0 %) variants. Among the different anatomic locations, TERT mutations were most frequent in the gallbladder (20.8 %), followed by perihilar (9.3 %), intrahepatic (7.7 %), and distal bile ducts (6.4 %) (p < 0.01). Genetically, TERT mutations were significantly associated with TP53 mutations (p = 0.04), ERBB2 amplification (p < 0.01), and high tumor mutational burdens (TMB) (p < 0.01); moreover, they were negatively correlated with KRAS (p < 0.01), SMAD4 (p = 0.01), and PBRM1 mutations (p = 0.01). In addition, TERT mutations were associated with a poor progression-free survival (PFS, p = 0.01). Specifically, in cases of intrahepatic cholangiocarcinoma, TERT mutations were more frequent in patients with cirrhosis (p = 0.01), hepatitis B virus infection (p = 0.04), and advanced disease stages (p < 0.01). In gallbladder carcinoma, TERT mutations were also associated with poor PFS. In conclusion, TERT mutations in biliary tract carcinomas had unique clinicopathologic and genetic characteristics. Despite its poor PFS, the concomitant presence of ERBB2 amplification and a high TMB indicated a potential for targeted therapy and immunotherapy in this specific subtype.

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.prp.2024.155806DOI Listing

Publication Analysis

Top Keywords

biliary tract
16
tert mutations
12
characteristics biliary
8
tract carcinomas
8
clinicopathologic genomic
4
genomic characteristics
4
biliary
4
tract
4
tert
4
carcinomas tert
4

Similar Publications

The Role of Sulfatides in Liver Health and Disease.

Front Biosci (Landmark Ed)

January 2025

Department of Surgery, School of Nutrition and Translational Research in Metabolism, Maastricht University, 6200 MD Maastricht, The Netherlands.

Sulfatides or 3-O-sulfogalactosylceramide are negatively charged sulfated glycosphingolipids abundant in the brain and kidneys and play crucial roles in nerve impulse conduction and urinary pH regulation. Sulfatides are present in the liver, specifically in the biliary tract. Sulfatides are self-lipid antigens presented by cholangiocytes to activate cluster of differentiation 1d (CD1d)-restricted type II natural killer T (NKT) cells.

View Article and Find Full Text PDF

To assess the clinical usefulness of teicoplanin optimized by means of a therapeutic drug monitoring (TDM)-guided approach for treating secondary bloodstream infections (BSIs) caused by . Hospitalized patients having in the period 1 March 2021-31 October 2024 a documented BSI caused by glycopeptide-susceptible being treated with teicoplanin as definitive targeted therapy optimized by means of a real-time TDM-guided expert clinical pharmacological advice (ECPA) program were retrospectively included. Teicoplanin trough concentrations (C) ranging from 20 to 30 mg/L were defined as the desired target of efficacy based on international guidelines.

View Article and Find Full Text PDF

Chronic hepatobiliary damage progressively leads to fibrosis, which may evolve into cirrhosis and/or hepatocellular carcinoma. The fight against the increasing incidence of liver-related morbidity and mortality is challenged by a lack of clinically validated early-stage biomarkers and the limited availability of effective anti-fibrotic therapies. Current research is focused on uncovering the pathogenetic mechanisms that drive liver fibrosis.

View Article and Find Full Text PDF

Lipid Metabolism Alterations in Hyperlipidemic Dogs with Biliary Tract or Endocrine Diseases.

Animals (Basel)

January 2025

Department of Veterinary Internal Medicine, College of Veterinary Medicine, Konkuk University, Seoul 05029, Republic of Korea.

Fasting hyperlipidemia results from lipid metabolism defects associated with alterations in specific lipoprotein classes. These changes may originate from genetic predispositions or underlying metabolic disorders, including cholestasis and endocrine diseases. This retrospective study aimed to analyze variations in lipoprotein electrophoresis (LPE) profiles in hyperlipidemic dogs and investigate the associations between biliary tract diseases, endocrine disorders, and lipid metabolism.

View Article and Find Full Text PDF

Biliary tract cancers (BTCs), including gallbladder and bile duct cancers, have a poor prognosis. Recent advances in chemotherapy, such as using targeted drugs for specific gene mutations, have improved outcomes. Gemcitabine plus cisplatin chemotherapy has been the standard of care for the primary treatment of BTCs, but secondary treatment had not been established until recently.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!