Navigation Links
Abnormalities in new molecular pathway may increase breast cancer risk
Date:6/17/2013

PHILADELPHIA A new molecular pathway involving the gene ZNF365 has been identified and abnormalities in that pathway may predict worse outcomes for patients with breast cancer, according to data published in Cancer Discovery, a journal of the American Association for Cancer Research.

"Genomic instability is an increased tendency for abnormal changes in DNA, like the addition of extra copies of chromosomes, DNA breaks and mutations," said Ji-Hye Paik, Ph.D., assistant professor in the Department of Pathology and Laboratory Medicine at Weill Cornell Medical College in New York, N.Y. "Because these genetic abnormalities increase the chances for developing a tumor, it is fundamentally important to understand the molecular basis of genomic instability in cancer for prognosis and therapy."

Telomeres are segments at the end of the chromosome that protect the chromosome from deterioration. As the length of the telomeres shortens, they activate cell death, mediated by the tumor suppressor gene, p53. This process is critical in the suppression of cancer, and dysfunctional telomeres can cause chromosomal abnormalities and cancer.

Using cells designed to be cancer-prone because of defective telomeres, Paik and colleagues demonstrated that p53 activates ZNF365 to maintain genomic stability. The researchers found that cells deficient in ZNF365 showed signs of incomplete doubling of DNA, causing abnormal cell division and unequally divided chromosomes. They concluded that because ZNF365 promotes the timely resolution of cell division, its loss led to an abnormal number of chromosomes called aneuploidy, which is implicated in many diseases including cancer.

"Our study is the first to demonstrate molecular mechanisms underlying the p53ZNF365telomere pathway and to show how alterations in this pathway may lead to increased cancer risk," said Paik. "Understanding this pathway provides novel therapeutic opportunities for cancers."

To understand the role of ZNF365 in cancer, Paik and colleagues used data available from The Cancer Genome Atlas (TCGA) and analyzed the expression of ZNF365 in 49 triple-negative breast cancers (TNBCs) the most aggressive form of breast cancer and 300 non-TNBCs. They found that expression of ZNF365 was lowest in TNBCs, and it remained high in non-TNBCs.

Using data from a larger cohort of 2,978 women from TCGA, the researchers also found that among women who had a 10-year, relapse-free survival, those with a high expression of ZNF365 had a 26 percent higher survival advantage. Further, when the researchers analyzed for the presence of ZNF365 in a tissue microarray containing 18 normal breast tissues, 141 TNBCs and 145 non-TNBCs, ZNF365 was present in normal breast tissues and non-TNBCs, but its expression declined in TNBCs.

According to Paik, this study is the first to determine the expression of ZNF365 in different types of breast cancers, and because it predicts disease prognosis, ZNF365 may be a potential biomarker for patient stratification.


'/>"/>

Contact: Jeremy Moore
jeremy.moore@aacr.org
215-446-7109
American Association for Cancer Research
Source:Eurekalert

Related medicine news :

1. Epilepsy Leads to More Brain Abnormalities Over Time
2. Insecticide Linked to Brain Abnormalities in Kids
3. Genetic abnormalities in benign or malignant tissues predict relapse of prostate cancer
4. Treatment of childhood OSA reverses brain abnormalities
5. Genome-wide analysis shows previously undetected abnormalities in parents of affected children
6. Gene Mutation Linked to Facial, Skull Abnormalities
7. Brain Scans of Hoarders Show Unique Abnormalities
8. Documenting womens experiences with chromosome abnormalities found in new prenatal test
9. Epigenomic abnormalities predict patient survival in non-Hodgkins lymphoma
10. Veterans with mild traumatic brain injury have brain abnormalities
11. MRI shows brain abnormalities in migraine patients
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... 2017 , ... As health professionals work to improve their approach to healthcare, ... doing more than filling out a survey; in many cases health professionals and patients ... health care and research on the importance of active engagement with patients and members ...
(Date:10/13/2017)... ... 2017 , ... PurhealthRX , a leading Health and Nutrition Company, is ... to full spectrum CBD oil will revolutionize the rapidly growing CBD market by reducing ... easily incorporated into liquid products, while reducing costs to end users. , The team ...
(Date:10/13/2017)... , ... October 13, 2017 , ... Many families have ... many long-term care insurance companies have a waiver for care if the client has ... period, when the family pays for care, is often waived, so the benefits from ...
(Date:10/13/2017)... ... October 13, 2017 , ... Yisrayl Hawkins, Pastor and Overseer ... one of the most popular and least understood books in the Holy Scriptures, Revelation. ... descriptions that have baffled scholars for centuries. Many have tossed it off as mere ...
(Date:10/13/2017)... ... ... “America On The Brink”: the Christian history of the United States and the ... published author, William Nowers. Captain Nowers and his wife, Millie, have six children, ... in the Navy. Following his career as a naval aviator and carrier pilot, ...
Breaking Medicine News(10 mins):
(Date:10/11/2017)... Oct. 11, 2017  True Health, a leader ... its effort during National Breast Cancer Awareness month ... risks. Research ... calculated that more than 10 million American women ... in BRCA1 or BRCA2 and have not had testing. ...
(Date:10/5/2017)... 2017  In response to the nationwide opioid ... Surgeons (AAOMS) released prescribing recommendations that urge ibuprofen ... as a first-line therapy to manage a patient,s ... Recognizing the value and importance of ... Prescribing: Acute and Postoperative Pain Management" stresses that ...
(Date:10/2/2017)... 2017  Eli Lilly and Company (NYSE: ... third quarter of 2017 on Tuesday, October 24, 2017. ... day with the investment community and media to further ... call will begin at 9 a.m. Eastern time. Investors, ... webcast of the conference call through a link that ...
Breaking Medicine Technology: