Cholangiocarcinoma Study

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.