We also examined our dataset for novel variants in genes known to be associated with cancer risk. We found 13 unique variants in 6 genes from 17 samples. This included frameshift, stop-gained and essential splice-site mutations in BRCA2 (n = 9), BRCA1 (n = 1), ATM (n = 2), BLM (n = 1), NBN (n = 2) and PMS2 (n = 2) (Fig. 3d and Supplementary Table 4e). Of the two PMS2 essential splice variants, one was found in a Korean sample. Loss-of-function mutations in PMS2 are associated with mismatch repair defects that lead to a higher risk of cancer development. In a separate study of gall bladder cancer, we found the same essential splice site PMS2 mutation (chromosome 7:6043690C>G) in a Korean patient whose gall bladder cancer exhibits microsatellite instability (E.W.S. and S. Seshagiri, manuscript in preparation). Identification of genetic variants that affect drug efficacy and safety through the alteration of pharmacokinetics enables application of individualized treatment36–41. Variation in drug responses are generally recognized and recommendations for dosing are sometimes guided by apparent or self-reported population identity despite the
