Genetic changesand the same types of mutations cause cancer only in certain organs of the human body, according to new research. German cancer researchers have shown that cells from different organs are differently susceptible to activating mutations in cancer pathogens. The same mutation in progenitor cells of the pancreas or bile duct leads to fundamentally different types of cancer.
Identical types of mutations cause different types of cancer
The authors of the new study discovered for the first time that tissue-specific genetic interactions are responsible for the different susceptibility of the biliary and pancreatic epithelium to transformation by oncogenes. The new findings could lead to more precise treatment decisions in the future. The research team examined the development of biliary tract and pancreatic cancer in mice. They replaced the normal oncogenes PIK3CA and KRAS with a mutation identical to that found in human cancers. Expression of these oncogenes in the common progenitor cells of the extrahepatic bile duct and pancreas led to very different results. Mice with the mutated PI3K gene developed mainly biliary tract cancer. Instead, only pancreatic cancer was observed in the animals with the mutated KRAS gene. This was unexpected because both genes are mutated in both human cancers.
The study results showed how genes work together to cause cancer in different organs. The team has identified the key players and the order in which they appear during tumor development. In addition, they were able to uncover the molecular processes by which normal cells are transformed into threatening cancers. Some cooperating genetic events driving identical types of mutations activate the PI3K pathway and become carcinogenic. Others disrupt regulatory proteins, inactivating their ability to suppress cancer progression. These findings have important implications for therapeutic interventions. Several tissue-specific genetic interactions drove cancer progression, according to the study authors.This studyshows that no single gene can predict a cancer's response to a particular therapy. In the future, it will be crucial to mechanistically understand the tissue-specific determinants of therapeutic response and resistance to take precision medicine to the next level.
