It was speculated that p53 function was lost by TP53 germline mutation with the loss of a wild type allele induced by the chemotherapy against ovarian cancer, leading to the development of MDS.
In this study, we focused on serous ovarian cancer, which is the most prevalent histological type, and performed immunohistochemical analysis to examine the expression of p21(WAF1/CIP1) and p53 in 43 cases of serous-type EOC sourced from a single University Hospital: 14 stage I, 4 stage II, 21 stage III, and 4 stage IV.
Furthermore, dominant-negative Akt sensitizes ovarian cancer cells to CDDP (10 micro M), an effect that is absent in cells expressing mutant p53 or treated with the p53 inhibitor pifithrin-alpha-hydrobromide (30 micro M) but restored by exogenous wild-type p53.
We have extended our LOH analysis of chromosome 3p to include 102 ovarian tumor specimens (29 and 73 samples were previously examined for LOH of chromosome 3p and 17 markers, respectively), using additional polymorphic markers, to assess the coordinate LOH of loci representing the three chromosome 3p minimal regions of deletions [von Hippel-Lindau syndrome (VHL), thyroid hormone receptor beta, and fragile histidine triad (FHIT)] and LOH of other important loci [tumor protein 53 (TP53), breast cancer 1 early onset (BRCA1), breast cancer 2 early onset, retinoblastoma 1, ornithine carbamoyltransferase, and androgen receptor] or somatic mutations in TP53.
In the present study, we analyzed patients of 19 German families with early onset breast cancer and/or a family history of breast and/or ovarian cancer for the presence of mutations in BRCA1 and TP53.