Ovarian cancer detected in blood samples

November 19, 2002

Scientists at Johns Hopkins have successfully detected ovarian cancer using a blood test for DNA shed by tumors. The test is based on digital analysis of single nucleotide polymorphisms (SNP, or "snips"), in which investigators separate the two strands of code found in every gene to search for imbalances that are a hallmark of cancer cell DNA.

With 54 blood samples from late- and early-stage ovarian cancer patients, the Hopkins team used digital SNP analysis to find so-called "allelic imbalance" in 87 percent (13 out of 15) of early-stage ovarian cancers and 95 percent (37 out of 39) with late-stage disease. No allelic imbalance was detected in 31 blood samples from healthy individuals. The researchers also compared the type of allelic imbalance found in 17 of the samples with the corresponding tumor tissue and found that 15 of these had matching allelic imbalance patterns.

Details of the initial studies of the test are published in the November 20, 2002 issue of the Journal of the National Cancer Institute.

"Digital SNP appears to detect ovarian cancers very well and is far more precise than other available tests," says Ie-Ming Shih, M.D., Ph.D., pathologist and director of this study for the Kimmel Cancer Center at Johns Hopkins. But, Shih cautioned, digital SNP is too costly and labor intensive at present to serve as a general screening test. "Currently there still is no way to usefully screen all women for ovarian cancer," Shih says, although it might be useful for women at high risk.

The Hopkins group also is investigating ways of achieving the same accurate detection rate with a less costly, more efficient test that could be used on a broader scale for ovarian and a variety of other cancers, Shih says.

DNA released from dying cells has long been detectable in blood samples, using sensitive molecular technology. But to distinguish normal from cancerous DNA, Kimmel Cancer Center scientists analyzed both sets of genetic code in DNA sequences. The individual sets of code are called alleles. In normal cells, DNA's two alleles - one derived from the maternal copy of the gene and the other from the paternal copy - are balanced in their basic building blocks. Tumor cells, on the other hand, have an unequal ratio of maternal and paternal alleles. Digital SNP analysis counts the alleles present in each blood sample.

In the Hopkins study, investigators first measured the total amount of DNA in blood samples taken from 44 healthy individuals; 122 patients with a variety of cancers ranging from head and neck cancers to brain cancer, as well as the 54 ovarian cancer patients; and 164 patients with non-cancerous diseases such as diabetes and hypertension. They found that, compared with blood samples of healthy individuals, average amounts of total DNA more than doubled for those with non-cancerous disease (7 ng/mL) but were eight times greater in samples from all cancer patients (59 ng/mL).

"The problem with using the total amount of DNA in the blood without performing digital SNP is that they are not specific for cancer, as elevated DNA levels can be found in blood samples from patients without cancer," says Shih.

Next, singling out the ovarian cancer samples, Shih and his team found high total amounts of DNA in only 47 percent (7 of 15) early-stage ovarian cancers and 56 percent (22 of 39) with late-stage disease. Adding another test, employing a standard ovarian cancer protein marker (CA125) currently used to monitor disease, added little improvement in detection rates, Shih reported.

"A test based on digital SNP holds promise for improved detection in a wide range of cancers, as well as ovarian cancer, which is currently detected almost always when it is in late stages and difficult to treat," says Shih.

Ovarian cancer will strike an estimated 23,000 U.S. women and cause approximately 14,000 deaths this year. It ranks fifth in cancer deaths among women. Generally, ovarian cancer is "silent" until the cancer has spread. Women should consult their physicians if they experience pressure or fullness in the pelvis, abdominal bloating, or changes in bowel and bladder patterns that continue and/or worsen.

Funding for this research was provided by the National Cancer Institute and the Richard TeLinde Research Fund.

In addition to Shih, other Johns Hopkins participants in this research include Hsueh-Wei Chang, Shing M. Lee, Steven N. Goodman, Gad Singer, Sarah K. R. Cho, Lori J. Sokoll, Fredrick J. Montz, Richard Roden, Zhen Zhang, Daniel W. Chan, and Robert J. Kurman.

Chang, Hsueh-Wei et al, "Assessment of Plasma DNA Levels, Allelic Imbalance, and CA125 as Diagnostic Tests for Cancer," Journal of the National Cancer Institute, Nov. 20, 2002, Vol. 94, No. 22.
-end-
Photo available upon request.

On the Web:

Kimmel Cancer Center at Johns Hopkins: http://www.hopkinskimmelcancercenter.org
Johns Hopkins Kelly Gynecologic Oncology Service: http://womenshealth.jhmi.edu/gynonc/
Johns Hopkins Pathology Ovarian Cancer Web Site: http://ovariancancer.jhmi.edu/home.cfm

Johns Hopkins Medical Institutions' news releases are available on an EMBARGOED basis on EurekAlert at http://www.eurekalert.org and from the Office of Communications and Public Affairs' direct e-mail news release service. To enroll, call 410-955-4288 or send e-mail to bsimpkins@jhmi.edu.

On a POST-EMBARGOED basis find them at http://www.hopkinsmedicine.org

Johns Hopkins Medicine

Related Cancer Articles from Brightsurf:

New blood cancer treatment works by selectively interfering with cancer cell signalling
University of Alberta scientists have identified the mechanism of action behind a new type of precision cancer drug for blood cancers that is set for human trials, according to research published in Nature Communications.

UCI researchers uncover cancer cell vulnerabilities; may lead to better cancer therapies
A new University of California, Irvine-led study reveals a protein responsible for genetic changes resulting in a variety of cancers, may also be the key to more effective, targeted cancer therapy.

Breast cancer treatment costs highest among young women with metastic cancer
In a fight for their lives, young women, age 18-44, spend double the amount of older women to survive metastatic breast cancer, according to a large statewide study by the University of North Carolina at Chapel Hill.

Cancer mortality continues steady decline, driven by progress against lung cancer
The cancer death rate declined by 29% from 1991 to 2017, including a 2.2% drop from 2016 to 2017, the largest single-year drop in cancer mortality ever reported.

Stress in cervical cancer patients associated with higher risk of cancer-specific mortality
Psychological stress was associated with a higher risk of cancer-specific mortality in women diagnosed with cervical cancer.

Cancer-sniffing dogs 97% accurate in identifying lung cancer, according to study in JAOA
The next step will be to further fractionate the samples based on chemical and physical properties, presenting them back to the dogs until the specific biomarkers for each cancer are identified.

Moffitt Cancer Center researchers identify one way T cell function may fail in cancer
Moffitt Cancer Center researchers have discovered a mechanism by which one type of immune cell, CD8+ T cells, can become dysfunctional, impeding its ability to seek and kill cancer cells.

More cancer survivors, fewer cancer specialists point to challenge in meeting care needs
An aging population, a growing number of cancer survivors, and a projected shortage of cancer care providers will result in a challenge in delivering the care for cancer survivors in the United States if systemic changes are not made.

New cancer vaccine platform a potential tool for efficacious targeted cancer therapy
Researchers at the University of Helsinki have discovered a solution in the form of a cancer vaccine platform for improving the efficacy of oncolytic viruses used in cancer treatment.

American Cancer Society outlines blueprint for cancer control in the 21st century
The American Cancer Society is outlining its vision for cancer control in the decades ahead in a series of articles that forms the basis of a national cancer control plan.

Read More: Cancer News and Cancer Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.