In cancer research, combination searches are essential for understanding the complex genetic landscape of tumors and identifying potential therapeutic targets. BRAF and KRAS are two critical oncogenes frequently mutated in various cancers, and their mutations often drive tumor growth through the activation of the MAPK/ERK signaling pathway. While BRAF and KRAS mutations are typically mutually exclusive—meaning they rarely occur together in the same tumor—studying cell lines with either mutation provides valuable insights into their distinct roles in cancer biology and treatment responses.
Note: We are using BRAF and KRAS as an example to demonstrate how to perform a combination search for multiple genes. This method can be applied to other gene combinations to explore their co-occurrence or mutual exclusivity in cancer cell lines, providing a powerful tool for uncovering new insights into cancer biology and therapy development.
This combination search focuses on identifying cell lines with either BRAF or KRAS mutations, enabling researchers to:
● Compare the molecular and phenotypic differences between BRAF- and KRAS-driven cancers.
● Explore targeted therapies specific to each mutation (e.g., BRAF inhibitors for BRAF-mutant cancers and KRAS G12C inhibitors for KRAS-mutant cancers).
● Investigate the broader implications of MAPK/ERK pathway activation in cancer progression.
The animated graph shows the operations to identify 392 cell lines satisfying the search criteria:
● The combination search is accomplished by the use of logic operators OR.
● The two filters form the search criteria: (BRAF: & mutation = Driver) OR (BRAF: & mutation = Driver), which means either BRAF or KRAS carries a driver mutation.
● We observe that BRAF and KRAS mutations are mutually exclusive from the heatmap, and mutation details are in the table below the heatmap.
