In the Journals

Somatic mosaic mutations in ovarian cancer linked to chemotherapy exposure, age

Factors such as older age and chemotherapy receipt appeared associated with somatic mosaic mutations in women with ovarian cancer, according to study results published in JAMA Oncology.

Somatic mosaic mutations in the p53-inducible protein phosphatase gene PPM1D have been observed in the peripheral blood mononuclear cells of patients with breast cancer, lung cancer and ovarian cancer, according to study background. However, no cause or effect has been determined.

Elizabeth M. Swisher, MD, professor of gynecologic oncology at University of Washington and director of the Breast and Ovarian Cancer Prevention Program at Seattle Cancer Care Alliance, and colleagues hypothesized that somatic mosaic mutations were associated with exposure to chemotherapy. To test their theory, they performed parallel sequencing to quantitate mutations in the peripheral blood mononuclear cells of women with primary ovarian cancer (n = 412) or relapsed platinum-resistant ovarian cancer (n = 274).

Of those with primary ovarian cancer, 326 had not been exposed to chemotherapy, and five of these patients had a PPM1D mutation. Of the other 86 who had been exposed to chemotherapy, six had a PPM1D mutation.

Fifty-eight of patients with platinum-resistant ovarian cancer harbored a PPM1D mutation.

Overall, chemotherapy exposure appeared significantly associated with somatic mosaic PPM1D mutations (P < .001).

Among women who received chemotherapy, older age at blood draw also appeared to be a significant predictive factor of harboring a PPM1D mutation (recurrent ovarian cancer, OR = 17.24; 95% CI, 6.8-43.69; primary ovarian cancer after chemotherapy, OR = 4.82; 95% CI, 1.43-16.18).

In women with relapsed ovarian cancer, receipt of two or more chemotherapy treatments corresponded with increased somatic mosaic mutations in PPM1D (P = .02).

Somatic mosaic mutations in TP53 did not appear associated with chemotherapy exposure or age.

The researchers had access to peripheral blood mononuclear cell samples from 13 patients near diagnosis as well as after a median of two chemotherapy treatments. PPM1D mutations increased in 11 of these women, with TP53 mutations increasing in two.

“Given the relationship between prior chemotherapy, age and somatic mosaic mutations in PPM1D, long-term prospective studies appear to be required to determine whether PPM1D or TP53 somatic mosaic mutations by themselves actually confer an increased risk for primary or secondary neoplasms,” Swisher and colleagues wrote. – by Cameron Kelsall

Disclosure: Swisher reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.

Factors such as older age and chemotherapy receipt appeared associated with somatic mosaic mutations in women with ovarian cancer, according to study results published in JAMA Oncology.

Somatic mosaic mutations in the p53-inducible protein phosphatase gene PPM1D have been observed in the peripheral blood mononuclear cells of patients with breast cancer, lung cancer and ovarian cancer, according to study background. However, no cause or effect has been determined.

Elizabeth M. Swisher, MD, professor of gynecologic oncology at University of Washington and director of the Breast and Ovarian Cancer Prevention Program at Seattle Cancer Care Alliance, and colleagues hypothesized that somatic mosaic mutations were associated with exposure to chemotherapy. To test their theory, they performed parallel sequencing to quantitate mutations in the peripheral blood mononuclear cells of women with primary ovarian cancer (n = 412) or relapsed platinum-resistant ovarian cancer (n = 274).

Of those with primary ovarian cancer, 326 had not been exposed to chemotherapy, and five of these patients had a PPM1D mutation. Of the other 86 who had been exposed to chemotherapy, six had a PPM1D mutation.

Fifty-eight of patients with platinum-resistant ovarian cancer harbored a PPM1D mutation.

Overall, chemotherapy exposure appeared significantly associated with somatic mosaic PPM1D mutations (P < .001).

Among women who received chemotherapy, older age at blood draw also appeared to be a significant predictive factor of harboring a PPM1D mutation (recurrent ovarian cancer, OR = 17.24; 95% CI, 6.8-43.69; primary ovarian cancer after chemotherapy, OR = 4.82; 95% CI, 1.43-16.18).

In women with relapsed ovarian cancer, receipt of two or more chemotherapy treatments corresponded with increased somatic mosaic mutations in PPM1D (P = .02).

Somatic mosaic mutations in TP53 did not appear associated with chemotherapy exposure or age.

The researchers had access to peripheral blood mononuclear cell samples from 13 patients near diagnosis as well as after a median of two chemotherapy treatments. PPM1D mutations increased in 11 of these women, with TP53 mutations increasing in two.

“Given the relationship between prior chemotherapy, age and somatic mosaic mutations in PPM1D, long-term prospective studies appear to be required to determine whether PPM1D or TP53 somatic mosaic mutations by themselves actually confer an increased risk for primary or secondary neoplasms,” Swisher and colleagues wrote. – by Cameron Kelsall

Disclosure: Swisher reports no relevant financial disclosures. Please see the full study for a list of all other researchers’ relevant financial disclosures.