Gene mutation of bile duct cancer

The molecular mechanisms underpinning the development of metachronous tumors in the remnant bile duct following surgical resection of primary biliary tract carcinomas (BTCs) are unknown. This study aimed to elucidate these mechanisms by evaluating the clinicopathologic features of BTCs, the alterations to 31 BTC-related genes on targeted sequencing, and the aberrant expression of p53, p16, SMAD4, ARID1A and β-catenin on immunohistochemistry. Twelve consecutive patients who underwent resection of metachronous BTCs following primary BTC resection with negative bile duct margins were enrolled...

Alagille syndrome (AGS) is a genetic disorder due to mutations in the JAGGED 1 or NOTCH 2 genes leading to multisystemic manifestations. Though these patients are at risk of developing various liver tumours, no cases of hepatoblastoma among young children with cirrhosis in AGS have been reported. We report a male toddler, with cirrhosis due to AGS who developed a hepatoblastoma. He underwent a liver transplant for decompensated chronic liver disease with marked pruritus, very high alpha-fetoprotein levels and malignant liver lesions on positron emission tomography CT...

Cholangiocarcinoma (CCA) is an aggressive bile duct malignancy with poor prognosis. To improve our understanding of the biological characteristics of CCA and develop effective therapies, appropriate preclinical models are required. Here, we established and characterized 12 novel patient-derived primary cancer cell (PDPC) models using multi-region sampling. At the genomic level of PDPCs, we observed not only commonly mutated genes, such as TP53, JAK3, and KMT2C, consistent with the reports in CCA, but also specific mutation patterns in each cell line...

Hepatoblastoma (HB) is an uncommon malignant liver cancer primarily affecting infants and children, characterized by the presence of tissue that resembling fetal hepatocytes, mature liver cells or bile duct cells. The primary symptom in affected children is abdominal lumps. HB constitutes approximately 28% of all liver tumors and two-thirds of liver malignancies in the pediatric and adolescent population. Despite its high prevalence, the underlying mechanism of HB pathogenesis remain largely unknown. To reveal the genetic alternations associated with HB, we conducted a comprehensive genomic study using whole-genome sequencing (WGS) and RNA sequencing (RNA-seq) techniques on five HB patients...

Objective: To explore the biological role and clinical significance of ubiquitin-specific protease 7 (USP7) in the carcinogenesis of scar ulcer. Methods: A retrospective observational study combined with bioinformatics analysis was used. The RNA expression profile data of USP7 in tumor and/or its corresponding paracancular normal tissue were obtained from The Cancer Genome Atlas (TCGA) database and the Gene Expression Omnibus database, and the RNA sequencing data were transformed by log2 . The variations of USP7 gene were analyzed by cBioPortal database...

BACKGROUND: Biliary atresia (BA) is poorly understood and requires liver transplantation (LT) in most children with lifelong risks of immunosuppression. AIMS & METHODS: To determine its genetic basis, we performed GWAS in 811 European BA cases treated with LT in US, Canadian and UK centers, and 4654 genetically matched controls. Whole genome sequencing of 100 cases evaluated synthetic association with rare variants. Functional studies included whole liver transcriptome analysis of 64 BA cases and perturbations in experimental models...

BACKGROUND: Cholangiocarcinoma (CCA) is a devastating malignancy and has a very poor prognosis if tumors spread outside the liver. Understanding the molecular mechanisms underlying the CCA progression will likely yield therapeutic approaches toward treating this deadly disease. AIM: To determine the molecular pathogenesis in CCA progression. METHODS: In silico analysis, in vitro cell culture, CCA transgenic animals, histological, and molecular assays were adopted to determine the molecular pathogenesis...

BACKGROUND: Systemic chemotherapy or chemoradiation therapy has proven to be effective in treating advanced biliary tract carcinoma (BTC). However, its efficacy in the adjuvant setting remains controversial. Therefore, this study aimed to determine the prognostic significance of genomic biomarkers in resected BTC and their potential role in stratifying patients for adjuvant treatment. METHODS: We retrospectively reviewed 113 BTC patients who underwent curative-intent surgery and had available tumor sequencing data...

The most common cause of mortality and disability globally right now is cholangiocarcinoma, one of the worst forms of cancer that may affect people. When cholangiocarcinoma develops, the DNA of the bile duct cells is altered. Cholangiocarcinoma claims the lives of about 7000 individuals annually. Women pass away less often than men. Asians have the greatest fatality rate. Following Whites (20%) and Asians (22%), African Americans (45%) saw the greatest increase in cholangiocarcinoma mortality between 2021 and 2022...

BACKGROUND: Pancreatic ductal carcinoma (PDC) is a challenging diagnosis with a particularly poor prognosis, even after curative surgery (median survival: <30 months). The prognosis of borderline resectable pancreatic cancer (BR-PDC) is even worse. We describe a patient with BR-PDC who achieved stable disease with metronomic chemotherapy after refusing surgery. CASE PRESENTATION: A 75-year-old woman was presented with jaundice and epigastric pain. Imaging confirmed a mass in the pancreatic head encasing the superior mesenteric vein, with obstruction of the pancreatic and bile ducts...

Peri-hilar cholangiocarcinoma (pCCA) is chemorefractory and limited genomic analyses have been undertaken in Western idiopathic disease. We undertook comprehensive genomic analyses of a U.K. idiopathic pCCA cohort to characterize its mutational profile and identify new targets. Whole exome and targeted DNA sequencing was performed on forty-two resected pCCA tumors and normal bile ducts, with Gene Set Enrichment Analysis (GSEA) using one-tailed testing to generate false discovery rates (FDR). 60% of patients harbored one cancer-associated mutation, with two mutations in 20%...

Cholangiocarcinoma is a rare type of cancer. Futibatinib is an irreversible, potent, selective inhibitor of fibroblast growth factor receptors (FGFR 1-4). On September 30, 2022, the US FDA first approved futibatinib to treat adult patients with bile duct cancer whose disease is unresectable, locally advanced, or metastatic intrahepatic cholangiocarcinoma harboring fibroblast growth factor receptor 2 (FGFR2) gene mutations or other classes of rearrangements. The approval of this medicine was based on phase 3 clinical trial results including an overall response rate (ORR) of 42% and a duration of response (DoR) of 9...

BACKGROUND: Metastatic cholangiocarcinoma (CC), a form of gastrointestinal cancer that originates from the bile ducts, cannot be cured by currently available therapies, and is associated with dismal prognosis. In a previous case report, adoptive transfer of autologous tumor infiltrating lymphocytes (TILs), the majority of which recognized a tumor-specific point mutation, led to a profound and durable cancer regression in a patient with metastatic CC. Thus, more effective treatment for patients with this disease may be developed by using TILs that target cancer-specific mutations, but also other genetic aberrations such as gene fusions...

Biliary tract cancers (BTCs) are aggressive tumors of the biliary system, which are often diagnosed at the advanced stage with a dismal prognosis. Among BTC patients, germline or somatic breast cancer-related gene 1/2 (BRCA1/2) mutation has been reported and the use of poly(ADP-ribose) polymerase inhibitor (PARPi) has achieved a certain effect, with no obvious severe side effects. The frequencies and mutated types of BRCA1/2 in advanced BTCs vary among studies. BRCA1 and BRCA2 play distinct roles in the development of BTC regardless of age or gender difference...

INTRODUCTION: Tumor-derived free-circulating DNA in peripheral blood allows the study of the molecular genetic profile in cholangiocarcinomas and even the effective monitoring of the response to chemotherapy. OBJECTIVE: The use of a liquid biopsy is a favourable solution, as repeated invasive histological sampling is much more practicable and avoidable. The efficiency of liquid biopsy-based sequencing increases with tumor progression and thus with the release of larger amounts of free DNA...

Poor prognosis of pancreaticobiliary malignancies is attributed to intrinsic biological aggressiveness and the lack of reliable methods for early diagnosis. This study aimed to evaluate the feasibility and availability of pancreatic juice- and bile-derived cell-free DNA (cfDNA) for diagnosing pancreaticobiliary stricture s . From October 2020 to February 2022, pancreatic juice or bile was obtained from 50 patients with pancreaticobiliary strictures during endoscopic retrograde cholangiopancreatography. cfDNAs extracted from the samples were analyzed using next-generation sequencing and a cancer gene panel...

BACKGROUND: SMAD4 is a key mediator of TGFβ signaling and one of the mutated genes in extrahepatic bile duct cancer (eBDC). It has been also reported that SMAD4 has dual functions, in carcinogenesis via silencing and in tumor invasion/metastasis via signaling, depending on tumor stage. We previously visualized more nuclear transitioning functional SMAD4 at the tumor invasion front than the central lesion. So, we investigated the localization of functional SMAD4 (e.g., invasion area or metastasis lesion) and its association with chemotherapy and chemo-radiation therapy...

Biliary duct brushing cytology is the standard of care for the assessment of bile duct strictures but suffers from low sensitivity for the detection of a high-risk stricture. Pathologic diagnosis of strictures is optimized by integration of cytomorphology and molecular analysis with fluorescence in situ hybridization or next-generation sequencing. Bile duct cancers are genetically heterogeneous, requiring analysis of multiple gene panels to increase sensitivity. Using molecular analysis as an ancillary test for bile duct brushing samples aids in the identification of mutations that support the diagnosis of a high-risk stricture as well as the identification of actionable mutations for targeted therapies currently in clinical trials for the treatment of patients with bile duct cancer...

Cholangiocarcinoma (CHOL) is highly malignant and has a poor prognosis. This study is committed to creating a new prognostic model based on hypoxia related genes. Here, we established a novel tumor hypoxia-related prognostic model consisting of 6 hypoxia-related genes by univariate Cox regression and the least absolute shrinkage and selection operator (LASSO) algorithm to predict CHOL prognosis and then the risk score for each patient was calculated. The results showed that the patients with high-risk scores had poor prognosis compared with those with low-risk scores, which was verified as an independent predictor by multivariate analysis...

Biliary cancer (BC) is a rare disease. It is formed from the biliary epithelium of the small ducts in the liver periphery (intrahepatic) and the main ducts of the hilum (extrahepatic). The incidence of intrahepatic carcinoma is rising in the western world, and the incidence of gallbladder cancer is declining. Surgical treatment is the primary treatment option for localized forms of these tumors, but only a small group of patients is eligible for it. Palliative therapy is the standard treatment option for those with advanced cases, and it mainly relies on chemotherapy...