In addition the patients must have evaluable or measurable disease by clinical or radiological studies. Alternatively, in the absence of radiologically evaluable or measurable disease, two sequentially rising marker values each one week apart attributed by treating phys ician to germ cell tumor was permitted. either beta HCG above 50 than mIU ml and or AFP above 20 ng ml qualified as eligible. A major exclusion was prior VEGFR PDGFR inhibitor therapy. Treatment plan Once registered, treatment was started no later than 7 days. Patients were treated with sunitinib malate Inhibitors,Modulators,Libraries 50 mg orally daily for 4 weeks every 6 weeks. A cycle was defined as a planned 6 week treatment interval. It was preferred that patients complete at least 2 cycles of therapy unless there is evidence of rapid disease progression.

Response evaluations were performed every 6 weeks according to RECIST criteria. The University of Texas MD Anderson cancer IRB approved this clinical trial and all Inhibitors,Modulators,Libraries patients were followed according to the protocol. The trial was an investigator initiated single institutional trial supported by Pfizer inc. which provided Sunitinib to the patients enrolled on the trial was closed early due to slow accrual. Next generation sequencing Next generation targeted exomic sequencing was per formed for genomic profling. 200 500ug of genomic DNA from each sample was sheared by sonication using the Cov aris E220 instrument. Library preparation utilized the KAPA kit following the with beads manufacturer protocol using KAPA HiFi polymerase. The cap ture included all exons from 202 cancer related genes.

Inhibitors,Modulators,Libraries Bio tin labeled DNA probes Inhibitors,Modulators,Libraries were designed using Roche Nimblegen for capturing target regions and followed manufactures protocol for the capture process. Probes were tiled at a minimum coverage of 2�� and balanced across the target re gions to ensure uniformity. Captured libraries were se quenced on a HiSeq 2000 on a version 3 TruSeq paired end flowcell according to manufacturers instructions The resulting BCL files con taining the sequence data were converted into. fastq. gz files and individual libraries within the samples were demultiplexed using CASAVA 1. 8. 2 with no mismatches. Deep sequencing data was aligned to to hg19 using BWA. Duplicate reads were removed via Picard. Single nucleotide variant, small indels and and copy number alterations were called using an in house pipeline or a previously published algorithm, respectively.

This supported identifying genome aberrations by next generation sequencing based assays to identify genomic alterations in 200 cancer Inhibitors,Modulators,Libraries related genes. Copy number validation The validation of the copy number alterations, was done using the OncoScan, a MIParray V3. technology. Results Five patients are enrolled Vandetanib mechanism of action into this Phase II study. their clinical characteristics are reported in Table 1.