Utility of the JAX Clinical Knowledgebase in capture and assessment of complex genomic cancer data

Cancer genomic data is continually growing in complexity, necessitating improved methods for data capture and analysis. Tumors often contain multiple therapeutically relevant alterations, and co-occurring alterations may have a different influence on therapeutic response compared to if those alterations were present alone. One clinically important example of this is the existence of a resistance conferring alteration in combination with a therapeutic sensitizing mutation. The JAX Clinical Knowledgebase (JAX-CKB) ( https://ckb.jax.org/ ) has incorporated the concept of the complex molecular profile, which enables association of therapeutic efficacy data with multiple genomic alterations simultaneously. This provides a mechanism for rapid and accurate assessment of complex cancer-related data, potentially aiding in streamlined clinical decision making. Using the JAX-CKB, we demonstrate the utility of associating data with complex profiles comprising ALK fusions with another variant, which have differing impacts on sensitivity to various ALK inhibitors depending on context. Database: Online resource captures complex genomics to guide drug decisions An online repository of genomic and clinical data offers a powerful tool for oncologists to tailor therapeutic decision-making to the complex molecular landscape of a patient’s tumor. Susan Mockus and colleagues from the Jackson Laboratory for Genomic Medicine in Farmington, Connecticut, USA, describe the concept of a ‘complex molecular profile’ included in the JAX Clinical Knowledgebase of curated data on genomic determinants of response to anti-cancer agents. This concept allows researchers to tie therapeutic outcomes data to many different genomic alterations at once. As a proof of concept, the researchers used the knowledgebase to look at tumor sensitivity to ALK inhibitors — drugs that block common gene fusions involving ALK . They showed that the impact of resistance-conferring mutations depended on the nature of ALK ’s fusion partner. The findings highlight the importance of considering all relevant genomic changes when choosing a course of therapy.