TCGA's Study of Pancreatic Ductal Adenocarcinoma
What is pancreatic cancer?
Pancreatic ductal adenocarcinoma is the most common form of pancreatic cancer, making up more than 80% of cases.1 The disease begins in the cells of the pancreas’s ducts, which transport juices containing digestive enzymes into the small intestine.2
Pancreatic cancer is the fourth most common cause of global cancer-related deaths and is almost always fatal.1 In 2012, it was estimated that around 44,000 new cases of pancreatic cancer were diagnosed and more than 37,000 deaths from this disease occurred in the United States alone, affecting both men and women.3
Pancreatic cancer posed a particular challenge for TCGA. While all cancerous tumors are comprised of a mix of normal and cancerous cells, pancreatic tumors contain a relatively low percentage of cancerous cells. TCGA imposed strict requirements on only accepting tumor samples with a high percentage of cancerous cells, as this produces higher quality data. For this disease, TCGA relaxed this criteria and instead, developed bioinformatic methods to deconvolute the data. Additional information on pancreatic cancer.
What have TCGA researchers learned about pancreatic ductal adenocarcinoma?
- Additionally, TCGA developed and employed deep and targeted genomic analysis techniques to study pancreatic cancer, which is particularly difficult to study because pancreatic tumors often have a low percentage of cancer cells compared to cells from normal or surrounding tissue.
- KRAS and the RAS-MAPK signaling pathway are key to understanding pancreatc cancers.
- The gene KRAS, which encodes an important signaling protein involved in cell growth and cell death, was mutated in 93% of cancers in the study.
- 60% of cancers studied that did not harbor a KRAS mutation had a mutation in a different gene in the RAS-MAPK signaling pathway.
- RREB1, another member of the RAS-MAPK pathway, may also promote pancreatic cancer when mutated.
- 42% of tumors studied had a genomic alteration that may qualify for a current clinical trial
- Identified signatures of microRNAs, long noncoding RNAs, and DNA methylation characteristic of basal-like and classical subtypes of pancreatic cancer.
1Hariharan D, Saied A, and Kocher HM. Analysis of mortality rates for pancreatic cancer across the world. HPB (Oxford). 10(1):58-62.
2The National Cancer Institute. What you need to know about cancer of the pancreas. www.cancer.gov/cancertopics/wyntk/pancreas. Accessed July 2010.
3American Cancer Society. Cancer Facts and Figures 2012. Atlanta: American Cancer Society, Inc. 2012.