Mutations in COPA gene: Expectations for applications in diagnostic and therapeutic methods
The 5-year relative survival rate exceeds 60 percent for cancer patients overall but is only around 35 percent for patients with small intestinal cancer. Small intestinal cancer is thought to develop from small intestinal adenomas, which are precancerous lesions. However, whereas APC gene mutations are found in around 90 percent of small intestinal adenomas, they are present in only about 30 percent of small intestinal cancers. As a result, the mechanisms by which small intestinal cancers lacking APC gene mutations develop have remained largely unclear.
A research team led by Professor Toshiro Sato of Keio University School of Medicine focused on the observation that while most small intestinal adenomas have a flat appearance, some exhibit an elevated morphology. The group analyzed the genomes of three elevated adenomas using next-generation sequencing. From this, they found that although none of the three cases carried APC gene mutations, all harbored mutations in the COPA gene. Cancer typically develops when abnormal cells escape elimination by the host defense system and continue to proliferate. Previous studies on cancers have shown that most classic oncogenes directly promote cell growth. COPA, however, serves a very different function, acting as a molecule that transports proteins within cells. The research team demonstrated that introducing COPA mutations into cultured normal intestinal tissues can drive tumor formation. They also found that some tumors carrying COPA mutations are more likely to progress to small intestinal cancer and that these tumors exhibit dependence on specific growth factors.
These findings, which uncovered a new pathway by which small intestinal adenomas develop into cancer, are expected to lead to new diagnostic and therapeutic approaches. In addition, small intestinal tissue cells engineered to carry COPA mutations are expected to serve as a valuable tool for future research.
(Article: Masanori Nakajo)
