Single test for many cancer mutations

U. WASHINGTON-SEATTLE (US) — More patients with ovarian cancer carry mutations predisposed to cancer—and in more genes—than previously thought.

A rapid experimental method for screening genomes has located mutations in 12 genes for inherited cancers of the ovary, fallopian tubes, and peritoneum (the thin tissue lining the lower abdomen).

More than one-fifth of ovarian cancers arise in women with a familial predisposition, but relying on family history would have missed one-third of the cases, says Elizabeth Swisher, associate professor of obstetrics and gynecology at the University of Washington in Seattle.


The results of a recent study, published in Proceedings of the National Academy of  Sciences, have implications beyond the important identification of mutations linked to ovarian and related cancers, Swisher says.

A quick, low-cost genome analysis method her team developed soon could be applicable to patient testing for a broad range of all known breast, ovarian, colon, pancreatic, and melanoma gene mutations.  A single test might be able to screen a patient for susceptibility to all these cancers.

Also, the great number of specimens that the method can simultaneously analyze could allow for large scale, population studies of cancer-causing mutations.  Such studies would tell who is at risk for certain cancers and how to effectively target prevention.

Swisher and her team concentrated on ovarian cancer gene detection in trying this sequencing method because ovarian cancer is one of the most deadly to affect a woman’s reproductive system and is difficult to diagnose in its early stages.

Ovarian cancer and cancer of the peritoneum begin quietly.  Eventually vague symptoms appear, but they mimic seemingly benign conditions, like bloating.

“Most women are not diagnosed until the cancer has advanced to the point where the chances of a cure are small,” Swisher says.  “Women with early stage ovarian cancer have a better survival than those diagnosed with late stages, but current methods of detection are not effective.”

The lack of effective early detection is why Swisher and her research team are looking for a more complete genetic picture of ovarian and related cancers.  Learning the genetic mutations associated with these cancers could lead to tests to identify early on the women prone to these malignancies.

A quick, low cost, individual screening test for a variety of gene mutations linked to ovarian cancer would allow for effective preventive measures, the researchers say.  For example, a woman whose genetic profile indicates high risk could consider an operation to remove her ovaries and fallopian tubes.  This procedure has already been shown to decrease the overall death rate in women who have BRCA1 or BRAC2 mutations.

These particular mutations heighten the risk of ovarian as well as breast cancer.  As the current study shows, previously unknown mutations in other genes also occur in the population of women diagnosed with ovarian cancer.

New developments in cancer drugs that selectively wipe out cells containing certain genetic deficiencies is another major incentive for scientists to locate other mutations involved in ovarian cancer, Swisher notes.

For example, the new drug class called poly-ADP-ribose polymerase (PARP) inhibitors is lethal to cells missing chemicals produced by normal BRAC1 and BRAC2 genes. The PARP drugs are showing efficacy in treating ovarian cancers in patients with mutations in these genes.

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