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PARP-7 mutation associated with longer ovarian cancer survival
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Patients with ovarian cancer with gene amplification of the PARP-7 protein had longer OS than patients without it, suggesting the protein may play an important role in survival, according to study results presented at the Society of Gynecologic Oncology Annual Meeting on Women’s Cancer.
Poly (ADP-ribose) polymerases, known as PARPs, are related enzymes that organize the transfer of ADP-ribose to target proteins. PARP-1 and -2 repair DNA damage in cancer cells, enabling them to survive. PARP inhibitors prevent this DNA repair, causing cancer cell death.
However, specific functions of PARP-7 have not yet been determined.
“The PARP family is still a mystery and that is why we need to continue to research PARPs,” Lavanya H. Palavalli Parsons, MD, assistant instructor in the department of obstetrics and gynecology at UT Southwestern Medical Center in Dallas, said in a press release. “I feel like we are only seeing the tip of a huge iceberg which is on the verge of being uncovered with the influx of new knowledge about the PARP family.”
Palavalli Parsons and colleagues evaluated PARP-7 in high-grade ovarian cancer using The Cancer Genome Atlas database.
Researchers created an analog-sensitive PARP-7 protein to discover proteomics of PARP-7 in relation to ovarian cancer. They also created an analog of 10 different PARP-7 mutations to bind with a fluorophore attached to positive nicotinamide adenine dinucleotide (NAD+), the substrate of PARP-7.
Researchers housed the 10 mutations in a viral expression system to infect insect cells to express PARP-7 protein and then selected the mutant that interacted with NAD+ analog to perform a large-scale reaction with ovarian cancer cells.
The Cancer Genome Atlas data showed patients with ovarian cancer with PARP 7 amplification, compared with those that did not, had a significant OS of 51 months versus 44 months (P = 0.028).
PARP-7 protein expression appeared highest if patients had genetic alterations in PARP-7 compared with no genetic alterations (95% CI, 49.65–535.2; P = .02).
Platinum-resistant patients without genetic alterations had a median OS of 3.3 months and PARP-7 expression level of 620.5 RSEM, whereas patients with alterations achieved a median OS of 11.7 months and demonstrated a PARP-7 level of 825.6 RSEM.
Platinum-sensitive patients without genetic alterations had a median OS of 14.7 months and PARP-7 expression level of 783.3 RSEM, whereas patients with alterations achieved a median OS of 36 months and demonstrated a PARP-7 level of 981.4 RSEM.
“If you took the specific patients who had alterations, they all had gene amplifications, which correlated with higher levels of expression of PARP-7,” Palavalli Parsons said. “These patients with ovarian cancer lived longer.”
In addition, mass spectrometry classified several extracellular matrix proteins as main targets for PARP-7.
“Identifying that PARP-7 modifies extracellular matrix protein helps understand the potential biology of PARP-7 significance to ovarian cancer,” the researchers wrote. – by Melinda Stevens
Reference:
Palavalli Parsons LH, et al. Abstract 18. Presented at: Society of Gynecologic Oncology Annual Meeting on Women’s Cancer; Mar. 24-27, 2018; New Orleans.
Disclosures: The authors report no relevant financial disclosures.