TP53 Gene Mutation Found in 80% of High Grade Ovarian Serous Carcinomas; TP53 Not Directly Involved In The Development of Drug Resistance

“… [T]he [Johns Hopkins] research team concluded that the frequency of TP53 gene mutations using purified tumor DNA from ovarian serous carcinomas was 80.3%, which is much higher than previously reported in the medical literature. Furthermore, the research team found that TP53 is not directly involved in the development of drug resistance in high-grade ovarian serous carcinomas.”

The TP53 gene mutation frequency in ovarian serous carcinomas has been reported to range between 50% and 80%. A research team working at the The Sidney Kimmel Comprehensive Cancer Center of The Johns Hopkins Medical Institutions (Johns Hopkins) made several important findings regarding TP53 gene mutations with respect to high grade ovarian serous carcinoma, as reported in the International Journal of Gynecological Cancer. Ovarian serous carcinoma is the most common tumor subtype within the epithelial ovarian cancer histological classification.

According to the Johns Hopkins research team, a stringent analysis of the TP53 gene using purified epithelial tumor samples has not been performed to accurately assess the TP53 gene mutation frequency and its correlation to tumor histologic grade. The research team assessed the TP53 gene mutational profile in a relatively large series of high-grade (53 primary tumors and 18 recurrent tumors) and 13 low-grade ovarian serous tumors. All samples were affinity purified, and the tumor DNA was analyzed for TP53 mutations in exons 4 through 9. In addition, the ovarian serous tumors were subjected to in vitro drug resistance testing. In vitro drug resistance assays were performed on the same tumor samples using carboplatin, cisplatin, paclitaxel, and taxotere, and the results were correlated with the TP53 mutation status.

The reported study findings are as follows:

  • TP53 mutations were detected in 57 (80.3%) of 71 high-grade carcinomas and in one (7.8%) of 13; low-grade serous tumors (an invasive low-grade serous carcinoma);
  • The mutations were predominantly missense mutations (59.6%);
  • TP53 mutations were associated with high-grade serous carcinomas and recurrent disease; and
  • There was no statistically significant correlation between TP53 mutation status and drug resistance assays or clinical stage.

Accordingly, the research team concluded that the frequency of TP53 gene mutations using purified tumor DNA from ovarian serous carcinomas was 80.3%, which is much higher than previously reported in the medical literature. Furthermore, the research team found that TP53 was not directly involved in the development of drug resistance in high-grade ovarian serous carcinomas.

Source: Assessment of TP53 mutation using purified tissue samples of ovarian serous carcinomas reveals a higher mutation rate than previously reported and does not correlate with drug resistance; Salani R, et. al., Int J Gynecol Cancer. 2008 May-Jun;18(3):487-91. Epub 2007 Aug 10.

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