Emerging findings from the most expansive studies of tumor genomes ever conducted are building a case for integrating all aspects of germline and somatic mutations into the analytical paradigm as a logical next step for precision oncology.
Historically, assigning clinical actionability to oncogenic drivers has focused on the somatic mutations unique to cancer cells. Germline mutations contained within the heritable genome have been largely consigned to heritable cancer risk management.
Table. Gene Mutations Targeted by FDA-Approved Companion Diagnosticsa9
Now, genome sequencing study findings are fostering a growing appreciation of both the burden of germline mutations and their potential clinical actionability. Furthermore, in both germline and tumor genomes, specific mutations have been identified in discordant histological cancer types. Pan-Cancer analyses have also revealed genetic interactions between germline and somatic mutations, suggesting that the germline genome may have a significant impact on the somatic evolution of the tumor.4-6
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