‘PapGene’ test detects endometrial and ovarian cancers

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Researchers have adapted the papanicolaou (Pap) smear test currently used to detect cervical cancer so that it can be used to screen women for endometrial and ovarian cancers.

"Our results demonstrate that mutant DNA molecules from most endometrial cancers and some ovarian cancers can be found in routinely collected Pap specimens," say Bert Vogelstein (Ludwig Center for Cancer Therapeutics, Baltimore, Maryland, USA) and colleagues. "These findings, in conjunction with technical advances allowing the reliable detection of mutations present in only a very small fraction of DNA templates, are the foundation of the PapGene test."

Currently proposed approaches for the early detection of endometrial and ovarian cancer such as transvaginal ultrasound and cytology have lacked specificity, failing to distinguish cancerous tissue from benign lesions or endometriosis, for example.

In their study, Vogelstein and team explored the possibility that somatic mutations characteristic of endometrial and ovarian cancers could be found in the DNA purified from liquid-based Pap smears. They reason: "Unlike cytologically abnormal cells, such oncogenic DNA mutations are specific clonal markers of neoplasia that should be absent in non-neoplastic cells."

The researchers acquired tumors from 46 cancer patients (24 endometrial cancer, 22 ovarian cancer) for whom Pap smear test specimens were available. Using whole-exome sequencing, the team assembled a panel of genes that are frequently mutated in the most common subtypes of the cancers and used this panel to search for mutations in the tumors.

Mutations were identified in all 46 samples, Vogelstein et al report in Science Translational Medicine.

The researchers then assessed the patients' Pap smear specimens and found that, for each of the 24 women with endometrial cancer, the same mutation was present in their Pap specimen as in their tumor sample. Among the 22 patients with ovarian cancer, the same mutation was found across the two specimen types in nine (41%) of 22 individuals.

However, "in a screening setting, the presence and genotype of tumors would obviously not be known before evaluation," note the researchers, who went on to design a prototype test that could amplify DNA segments from the mutated genes most commonly found in endometrial and ovarian cancers.

The team applied this test to the Pap specimens from 14 cancer patients (12 endometrial and two ovarian) as well as specimens from 14 healthy controls. The expected mutation was identified in all 14 of the cancer specimens, whereas no mutations were detected in the control specimens.

"PapGene testing has the capacity to increase the use of conventional cytology screening through the unambiguous detection of DNA from endometrial and ovarian carcinomas, and lays the foundation for a new generation of screening tests," conclude Vogelstein et al.

Licensed from medwireNews with permission from Springer Healthcare Ltd. ©Springer Healthcare Ltd. All rights reserved. Neither of these parties endorse or recommend any commercial products, services, or equipment.

Sally Robertson

Written by

Sally Robertson

Sally first developed an interest in medical communications when she took on the role of Journal Development Editor for BioMed Central (BMC), after having graduated with a degree in biomedical science from Greenwich University.

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