The mutual exclusivity in serous tumors of CCNE1 amplification and somatic alterations affecting FBXW7
, which normally mediates the ubiquitin-mediated degradation of cyclin E, suggests that these genetic events are functionally redundant (16).
The mutations identified, listed in order of frequency, included TP53, KRAS, APC, FBXW7
, GNAS, BRAF, NRAS, PIK3CA, FGFR3, and SMAD4 (Figure 1).
The primers used target 207 hotspots covering 50 genes: ABL1, AKT1, ALK, APC, ATM, BRAF, CDH1, CDKN2A, CSF1R, CTNNB1, EGFR, ERBB2, ERBB4, EZF2, FBXW7
, FGFR1, FGFR2, FGFR3, FLT3, GNA11, GNAQ, GNAS, HNF1A, HRAS, IDH1, IDH2, JAK2, JAK3, KDR, KIT, KRAS, MET, MLH1, MPL, NOTCH1, NPM1, NRAS, PDGFRA, PIK3CA, PTEN, PTPN11, RB1, RET, SMAD4, SMARCB1, SMO, SRC, STK11, TP53, and VHL (Ion AmpliSeq Cancer Hopspot Panel v2; Life Technologies).
The most-common, potentially targetable alterations were mutations, amplifications, and homozygous deletions of PIK3CA (n = 8; 40%), PTEN (n = 5; 25%), CDKN2A/B (n = 4; 20%), CCND3 (n = 3; 15%), CCNE1 (n = 2; 10%), and EGFR (n = 2; 10%), with AKT3, CCND1, CCND2, CDK4, FBXW7
, FGFR1, HRAS, NF1, PIK3R1, and SRC altered in a single case (Figure 1; Table 1).