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Somatic Mosaic Mutations in PPM1D & TP53

What’s the association with chemo exposure?

Both chemotherapy exposure and age influenced the accumulation of PPM1D-mutated peripheral blood mononuclear cell (PBMS) clones in the blood of women with ovarian carcinoma. This according to a study of quantitative mutations in PBMCs of 686 women with primary ovarian cancer (n=412) or relapsed OC (n=274). Researchers found:

• The frequency of somatic mosaic PPM1D mutations in PBMCs was significantly associated with prior chemotherapy, and in patients exposed to chemotherapy, with older age at blood draw (recurrent OC odds ratio 17.24 and primary OC postchemotherapy OR, 4.82).

• In contrast, somatic mosaic mutations in TP53 were not significantly associated with chemotherapy or age.

• In sequential PBMC samples from 13 patients with OC near diagnosis and after a median of 2 different chemotherapy regimens, somatic mosaic PPM1D mutations increased in 11 individuals (84.6%) and TP53 mutations appeared in 2 (15.4%).

Citation: Swisher EM, Harrell MI. Norquist BM, et al. Somatic mosaic mutations in PPM1D and TP53 in the blood of women with ovarian carcinoma. [Published online ahead of print February 4, 2016]. JAMA Oncol. doi: 10.1001/jamaoncol.2015.6053.