PTEN, a tumor suppressor commonly mutated (50%) in endometrial carcinoma, is found mutated in endometrioid carcinoma of the ovary, but not in other forms of ovarian cancer.
A patient with V600E BRAF-mutant melanoma and another with platinum-refractory epithelial ovarian cancer exhibiting PTEN loss and PIK3CA amplification demonstrated partial response by RECIST and GCIG-CA125 criteria, respectively.
Although many tumors presented a single lesion (28/93, of which 23 overexpressed PIK3CA, 1 overexpressed AKT and 4 had lost PTEN), many OC (35/93) presented multiple alterations within the PI3K pathway.
Between 2002-2005, probands from 300 US families with 4 or more cases of breast or ovarian cancer but with negative (wild-type) commercial genetic test results for BRCA1 and BRCA2 were screened by multiple DNA-based and RNA-based methods to detect genomic rearrangements in BRCA1 and BRCA2 and germline mutations of all classes in CHEK2, TP53, and PTEN.
BRCA1 and BRCA2 mutations confer very high risks of breast and ovarian cancer. p53 and PTEN mutations lead to very high breast cancer risks associated with rare cancer syndromes.
Conditional homozygous knockout of PTEN mediated by PAX8-cre recombinase was sufficient to drive endometrioid and serous borderline ovarian carcinoma, providing the first model of FTE-derived borderline tumors.
Evidence of mutations in the tumour suppressor PTEN gene in the endometrioid subtype of epithelial ovarian cancer further suggests that somatic genetic alterations represent early events in the transformation of benign endometriotic cells.
Frequent loss of PTEN expression is linked to elevated phosphorylated Akt levels, but not associated with p27 and cyclin D1 expression, in primary epithelial ovarian carcinomas.
Grb2 depletion under non-stimulated conditions inhibits PTEN, promotes Akt-induced tumor formation and contributes to poor prognosis in ovarian cancer.
In these cases, there is a high frequency of atypia in the endometriosis, and the endometriosis and the associated ovarian carcinoma may show identical PTEN mutations.
It is for the purpose of this study to investigate its function and the mechanisms by which PTEN enhances the sensitivity of ovarian cancer to antitumor agents.
Overall, we suggest that miR-205 functions as an oncogenic miRNA by directly binding to SMAD4 and PTEN, providing a novel target for the molecular treatment of ovarian cancer.
PIK3CA amplification was seen in 54 of 152 (35.5%) EOC cases analyzed; PIK3CA gene mutations in 6/153 EOC (3.9%); KRAS mutations in 3/154 EOC (1.9%), BRAF mutations in 3/156 EOC (1.9%), p53 mutation in 50/154 EOC (32.5%), and loss of PTEN protein expression in 33/144 EOC (22.9%). p110 alpha overexpression was associated with increased phosphorylation of AKT-Ser 473 and with the proliferation marker Ki-67.
Reduced PTEN expression is a poor prognostic factor for DFS in patients with epithelial ovarian cancer who were treated with debulking surgery and postoperative taxane and platinum chemotherapy.