We next used ABSOLUTE to analyze the multiplicity of both the reference and alternate alleles, to classify point mutations as either heterozygous or homozygous in the affected cell-fraction (Fig. 5a-c). We considered 15 genes with mutations recently identified in these data 33, including 5 known tumor suppressor genes (TSGs) and 5 oncogenes (Fig. 5d). The frequency of homozygous mutations in known TSGs and oncogenes were significantly different, with a significantly elevated fraction of homozygous mutations in the TSGs (P = 0.006, Fig. 5d) and no homozygous mutations in the oncogenes: (P = 0.012, Fig. 5d). This result provides evidence supporting CDK12 as a candidate TSG in ovarian carcinoma 33, since 7 of 12 CDK12 mutations were homozygous (P= 6.5×10-5; Fig. 5d).
