Julie Grisham

As research has revealed more about the genomics of cancer, it’s changed the way that doctors think about the disease. There is not a single type of breast tumor or colon tumor, for example, but many variations of each kind of cancer. The differences are in tumors’ appearance under a microscope, their molecular signatures, and distinct changes that drive their growth.

This variety is also found with ovarian tumors. There are many types, and not all behave or respond to treatment in the same way. For a rare ovarian tumor called sclerosing stromal tumor (SST), the situation is even more complicated. SST is not cancer but a benign tumor that can be misdiagnosed as cancer.

“If a woman with SST is misdiagnosed as having ovarian cancer, she would likely be given more-aggressive treatments that she wouldn’t need,” says Britta Weigelt, a Memorial Sloan Kettering research scientist and senior author of a 

. “Although these tumors can cause a lot of pain and other symptoms, they can be successfully treated with surgery alone because they do not spread.”

In the study, the investigators reported that they had identified a unique molecular change in sclerosing stromal tumors. This allows for the accurate diagnosis of this tumor. They also say that some of the biological insights learned may be applicable to other kinds of tumors.

Sclerosing stromal tumors make up about 5% of an already rare type of ovarian tumor called sex cord-stromal tumor. Most of these tumors, which can also grow in the testes, are cancerous. Despite how uncommon sclerosing stromal tumors are, the researchers from MSK and their colleagues at Massachusetts General Hospital in Boston, as well as collaborators from outside the United States, were able to obtain 26 samples that were confirmed to be this type of tumor.

“This was, by a wide margin, the largest collection of these tumors ever studied with genetic approaches,” says Sarah Kim, the first author of the study and a fellow in Dr. Weigelt’s lab. “I completed four years of residency, and I never saw a single patient with it. There’s a lack of familiarity with (sclerosing stromal tumor) in the medical community.”

The type of change that drives sclerosing stromal tumor is called a fusion gene. Fusion genes occur when part of a chromosome breaks off and attaches to another part of a chromosome, linking two genes that are not normally linked. Fusion genes are found most commonly in pediatric tumors, especially sarcomas and blood cancers. Similarly, sclerosing stromal tumor also affects younger women — usually in their 20s or 30s.

In sclerosing stromal tumor, one of the genes involved in the fusion is called FHL2. The other gene is called GLI2. FHL2 is a gene that’s naturally expressed at high levels in ovarian tissue. When it fuses to GLI2, it drives the production of a tumor-causing protein.

 study, 21 of the 26 samples tested had GLI2 fusion genes. The investigators reviewed data for more than 9,000 tumors in a large database and didn’t find any other instances of a FHL2-GLI2 fusion gene, confirming that this fusion is unique to sclerosing stromal tumor.

Further research uncovered that the protein created from the fusion is involved in the Sonic hedgehog pathway. This signaling pathway is important for embryonic development. It has also been implicated in cancer, especially certain brain tumors and basal cell skin cancers.

When the researchers tested drugs that target the Sonic hedgehog pathway in sclerosing stromal tumor cell models in a dish, the cells responded, confirming that this pathway was driving cell growth.

“We started this project because (sclerosing stromal tumor) is a clinical conundrum,” Dr. Kim says. “These findings will make things easier for both doctors and patients, by making it simpler to identify this rare tumor.”

“This study also provides new biological clues about Sonic hedgehog and its role in cancer,” Dr. Weigelt says. “We hope that it may help in the understanding of other tumors that pose diagnostic and clinical challenges.”

Information provided by MSK (“Information”) is not intended as a substitute for medical professional help or advice but is to be used only as an educational aid in understanding current medical knowledge. A physician should always be consulted for any health problem or medical condition. Use of the Information is further subject to 

Articles

Investigators are studying a rare ovarian tumor called sclerosing stromal tumor, a benign tumor that can be misdiagnosed as cancer.

 

Unique Genetic Change Found in Rare Ovarian Tumor Could Spare Patients from Unnecessary Treatment

A lot has changed since the BRCA genes were discovered in the early 1990s. Mutations in 

ncer genes 1 and 2 — were the first specific genetic changes linked to cancers that run in families. These include 

 genes is more available and affordable than ever before.

 mutation status can help guide treatment decisions. It can also raise a red flag about the risk for developing additional cancers. Family members may consider testing as well, to see if they too have an increased cancer risk.

 showed that only about a quarter of women with breast cancer and a third of women with ovarian cancer in Georgia and California had received BRCA testing, it raised eyebrows in the cancer community.

“The rates of genetic testing observed in this study were eye-opening to the cancer genetics and oncology community. Testing rates were much lower than expected,” says 

, Clinical Director of MSK’s Clinical Genetics Service. “Importantly, the study uncovered both racial and socioeconomic disparities in genetic testing rates among women with ovarian cancer. For example, testing rates were far lower for black women than white women. They were also lower for uninsured than insured patients.”

Testing is important because certain targeted drugs may be effective against cancers driven by BRCA mutations.

“With the US Food and Drug Administration’s approval of a class of drugs called PARP inhibitors in both BRCA-associated advanced breast and ovarian cancers, we now know that women with these cancers can benefit from these targeted therapies,” Dr. Stadler says. “Moreover, having a germline

mutation increases the risk of a second cancer, which could be prevented with appropriate enhanced screening or risk-reducing surgery.” (Germline mutations are inherited at birth.)

Women who know they have these mutations may decide to undergo more extensive surgery, for example. This might include the removal of the unaffected ovary or breast.

Experts at MSK say that the study’s low numbers highlight the need for better education among healthcare providers and the general public about the importance of genetic testing and genetic counseling.

However, the numbers seen in this study are not representative of what happens at MSK, says 

. Since 2008, every woman who has come to MSK for 

 has been offered genetic testing. For women with breast cancer, MSK follows the guidelines laid out by the National Comprehensive Cancer Network to determine who would most benefit from genetic testing. Because breast cancer is a more common disease, the guidelines for who should be offered genetic testing are stricter.

The study’s authors noted that obstacles to genetic testing may have influenced low testing rates. These include lack of access to genetic testing, the cost of testing, and 

. Ms. Arnold Ross says that these can be roadblocks for people deciding to get tested no matter where they live. But strides have been made to make testing more accessible.

“These challenges happen everywhere,” she adds. “Out-of-pocket costs can vary, but the cost of genetic testing itself has gone down over the years as the technology has improved and the number of labs competing to run these tests has increased. This is due to peer-reviewed articles documenting the importance of genetic testing for certain people.”

Insurance coverage for genetic tests can also vary, but more and more insurers, including Medicare, are now covering or partially covering this testing. 

 can help ease some of the burden. At MSK, financial assistance is available for people who have genetic testing.

MSK also offers genetic counseling and testing for families that may be at risk. “When a woman has genetic testing and learns that she carries one of these mutations, it can be life-saving for her relatives as well,” Dr. Stadler says. “If they also test positive, they can greatly benefit from enhanced screening and prevention measures.” 

This article was originally published by Memorial Sloan Kettering Cancer Center, and it is subject to these 

A recent study found that only a quarter of women with breast cancer and a third of women with ovarian cancer had undergone genetic testing. Memorial Sloan Kettering experts say these numbers are surprisingly low.

Julie Grisham

Unique Genetic Change Found in Rare Ovarian Tumor Could Spare Patients from Unnecessary Treatment

Study Asks: Are Women Missing Out on BRCA Testing?

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