Oncogenic Mutations Found in Cervical Cancer

Marked differences have been found in the genomic environment of the two most common types of cervical cancer, suggesting that patients might benefit from therapies geared to each type's molecular characteristics.

The most common oncogenic mutations in cervical cancers have been studied and the genomic differences between the two most common histologic subtype, adenocarcinoma and squamous cell carcinoma have been explored.

Scientists at the Dana-Farber Cancer Institute (Boston, MA, USA) and their colleagues, probed the DNA of 80 cervical cancer tumor, 40 adenocarcinomas, and 40 squamous cell carcinomas, for 1,200 mutations in hundreds of genes linked to cancer. The probe was done with high-throughput genotyping platform called OncoMap, a system developed at Dana-Farber to test large numbers of tumor samples for 139 cancer-related genes.

The investigators found that 31.3% of the samples had phosphatidylinositol 3-kinase, catalytic subunit α (PIK3CA) mutations; 17.5% of the adenocarcinomas and none of the squamous-cell carcinomas had Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations; and 7.5% of the squamous cell carcinomas, but none of the adenocarcinomas, had a rare mutation in the gene epidermal growth factor receptor (EGFR). PIK3CA mutations were associated with a shorter survival period as patients whose tumors carried these mutations lived a median of 67 months after diagnosis compared with 90 months for patients whose tumors lacked the mutations.

Alexi A. Wright, MD, MPH, the senior author of the study, said, “We have historically treated cervical cancers as one disease. However, our findings suggest that some patients may be at higher risk of dying from their disease and might benefit from a more tailored treatment approach.” The authors noted that the discovery of high rates of PIK3CA mutations in the cervical tumor samples suggests that many patients could benefit from drugs known as phosphatidylinositide 3-kinase inhibitors, which target the family of proteins associated with the gene. Patients with the adenocarcinoma subtype of cervical cancer may benefit from targeted agents known as mitogen-activated protein kinase (MEK) inhibitors. The study was published on August 23, 2013, in the journal Cancer.

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Dana-Farber Cancer Institute