The expression of FBXW7 and substrates were studied in 296 invasive carcinomas by immunohistochemistry and disease-free survival was analyzed in a subset of patients treated with paclitaxel.
In vitro evidence indicates that Fbw7 ablation promotes genetic instability that is suppressed by p53, and we show that most Fbw7⁻/⁻; p53⁻/⁻ carcinomas exhibit a CIN⁺ phenotype.
We found frequent somatic mutations in TP53 (81.6%), PIK3CA (23.7%), FBXW7 (19.7%), and PPP2R1A (18.4%) among the 76 uterine serous carcinomas examined.
We assessed the role of CDC4/FBXW7 in gastric cancer, through loss of heterozygosity (LOH) and multiplex ligation-dependent probe amplification (MLPA) on 47 flow-sorted gastric carcinomas including early-onset gastric cancers (EOGC) and xenografted conventional gastric carcinomas.
These data indicate that hCDC4 mutation occasionally occurs in gastric carcinomas and suggest that it might play a role in the development of some gastric carcinomas.