CHAPTER 4 86 two tumors (both mixed uterine CCCs). The single POLE mutated (mixed) uterine CCC in addition harbored a TP53 mutation. Other mutation frequencies did not differ significantly between pure and mixed CCCs (Table 3). Within the whole study group, the following molecular subgroups were identified: POLE mutated in 1 patient (3%); MSI in 10 patients (28%); TP53 wildtype in 14 patients (39%) and TP53 mutated in 11 patients (31%). Analyzing pure and mixed uterine CCCs separately, the POLE mutated subgroup was found in respectively 0% and 6% of patients; the MSI subgroup in 6% and 50%; the TP53 wildtype subgroup in 56% and 22%; and the TP53 mutated subgroup in 39% and 22%, respectively (p = 0.013, Table 3). In ten patients with mixed uterine CCC, both components could be sequenced separately (Figure 1). In eight patients, at least one shared mutation was found (Supplementary C). A total of 13 mutations were found in both components (three ARID1A; one ERRB2; three PIK3CA; three PTEN; three TP53). A total of 26 mutations were only found in one of the components and can be seen as unique variants (one AKT1; twelve ARID1A; one MTOR; one NRAS; five PIK3CA; four PTEN; two TP53). Excluding patients with POLE mutated and MSI tumors, six mutations were found in both components, and only four mutations were only found in one of the components. 1E 1CC 3E 3CC 13E 13CC 17E 17CC 45SE 45CC POLE TP53 KRAS ARID1A PTEN PIK3CA NRAS AKT1 46E 46CC 55E 55CC 59E 59CC 69E 69CC 70SE 70CC ERBB2 MTOR MSI Not present deletion substitution duplication Figure 1. Display of all next-generation sequencing derived mutated genes in ten cases with mixed uterine clear cell carcinomas (CCCs) in which both component were sequenced separately. The colors indicate specific genes (see legend). Abbreviations: CC, clear cell; E, endometrioid; SE, serous; MSI, microsatellite instable.
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