We describe an approach for targeted genome resequencing, called 
oligonucleotide-selective sequencing (OS-Seq), in which we modify the 
immobilized lawn of oligonucleotide primers of a next-generation DNA sequencer 
to function as both a capture and sequencing substrate. We apply OS-Seq to 
resequence the exons of either 10 or 344 cancer genes from human DNA samples. In 
our assessment of capture performance, >87% of the captured sequence originated 
from the intended target region with sequencing coverage falling within a 
tenfold range for a majority of all targets. Single nucleotide variants (SNVs) 
called from OS-Seq data agreed with >95% of variants obtained from whole-genome 
sequencing of the same individual. We also demonstrate mutation discovery from a 
colorectal cancer tumor sample matched with normal tissue. Overall, we show the 
robust performance and utility of OS-Seq for the resequencing analysis of human 
germline and cancer genomes.