Whole-exome sequencing was performed by the Sequencing and Microarray Facility at MDACC using previously published methodology [19 (link)]. Briefly, libraries were prepared from Biorupter ultrasonicator (Diagenode)–sheared genomic DNA using the Agilent Technologies SureSelectXT Reagent Kit. Libraries were prepared for capture with 10 cycles of PCR amplification and then assessed for size distribution on the Fragment Analyzer using the High Sensitivity NGS Fragment Analysis Kit (Advanced Analytical) and quantity using the Qubit dsDNA HS Assay Kit (Thermo Fisher Scientific). Exon target capture was performed using the Agilent Technologies SureSelectXT Human All Exon V4 kit. Following capture, index tags were added to the exon-enriched libraries using 10 cycles of PCR. The indexed libraries were then assessed for size distribution and quantified using the Agilent Technologies 4200TapesStation and the Qubit dsDNA HS Assay Kit, respectively. Equal molar concentrations of libraries were multiplexed eight to nine samples per pool, and each pool was sequenced in one lane of the Illumina HiSeq4000 sequencer, using the 76nt paired end format.