What is cholangiocarcinoma?
Cholangiocarcinoma is a cancer that develops in the bile duct. The bile duct is a network of tubes that carry bile from the liver and gallbladder to the small intestine.1 Tumors that start in bile duct branches that lie inside the liver are called intrahepatic bile duct cancer,1 while those that form outside the liver are called extrahepatic bile duct cancer. About 10% of all cholangiocarcinoma are intrahepatic and 90% are extrahepatic.1 TCGA studied both subtypes of cholangiocarcinoma.
Although cholangiocarcinoma is a rare cancer, the incidence and mortality rates for the disease have been increasing worldwide in the last three decades.2 Between 2,000 and 3,000 Americans are diagnosed with cholangiocarcinoma each year,3 the majority of them with tumors at advanced stages.1 This cancer is more prevalent in Asia and the Middle East, where parasitic infection of the bile duct increases the risk of cholangiocarcinoma.1 Other diseases of the bile duct or liver, such as bile duct stones and liver disease, obesity, diabetes, and smoking are also risk factors.1 When intrahepatic and extrahepatic cholangiocarcinoma spread to other parts of the body, only 2% of patients survive five years after diagnosis.1 Additional information on bile duct cancer.
What have TCGA researchers learned about cholangiocarcinoma?
- The 38 cholangiocarcinoma tumors characterized by TCGA had alterations to known tumor suppressor genes and oncogenes:
- Alterations limiting the expression of tumor suppressor genes CDKN2, BAP1, and ARID1.
- Alterations increasing the expression of oncogenes FGFR2 and IDH1/2.
- Cholangiocarcinomas can by categorized into four subgroups based on their mRNA expression, patterns DNA methylation, and copy numbers of chromosome segments.
- A new subtype characterized by mutations in the IDH gene was identified.
- Cholangiocarcinoma tumors closely resemble a subset of liver cancers analyzed by a previous TCGA study, suggesting the two cancers may exist on a continuous spectrum.