Features Partner Sites Information LinkXpress
Sign In
Demo Company

Loss of STAG2 Gene Improves Bladder Cancer Prognosis

By BiotechDaily International staff writers
Posted on 23 Oct 2013
Print article
Image: This image shows a bladder tumor sample containing mutations in the STAG2 gene (Photo courtesy of the Spanish National Cancer Research Center).
Image: This image shows a bladder tumor sample containing mutations in the STAG2 gene (Photo courtesy of the Spanish National Cancer Research Center).
Results obtained during a study conducted by Spanish cancer researchers indicated that mutations of the STAG2 (stromal antigen 2) gene suppressed development of urothelial bladder cancer (UBC) by acting through mechanisms that were different from the gene's role in preventing aneuploidy.

The protein encoded by the STAG2 gene is a subunit of the cohesin complex, which regulates the separation of sister chromatids during cell division. Targeted inactivation of this gene results in chromatid cohesion defects and aneuploidy, suggesting that genetic disruption of cohesin is a cause of aneuploidy in human cancer.

Bladder cancer represents a serious public health problem in many countries, especially in Spain, where 11,200 new cases are recorded every year, one of the highest rates in the world. The majority of these tumors have a good prognosis for five-year survival after diagnosis, and most have not infiltrated the bladder muscle at the time of diagnosis.

Investigators at the Spanish National Cancer Research Center (Madrid) performed an exome sequencing study to identify genes linked to noninfiltrating bladder cancer. They analyzed the exome from 17 bladder cancer patients and subsequently validated the data by the analyzing a specific group of genes in 60 additional patients.

Results published in the October 13, 2013, online edition of the journal Nature Genetics revealed a set of previously unidentified genes mutated in these tumors coding for proteins involved in chromatin modification (MLL2, ASXL2, and BPTF), cell division (STAG2, SMC1A, and SMC1B) and DNA repair (ATM, ERCC2, and FANCA). STAG2 was significantly and commonly mutated or lost in UBC, mainly in tumors of low stage or grade, and its loss was associated with improved outcome.

Loss of STAG2 expression was often observed in chromosomally stable tumors, and STAG2 knockdown in bladder cancer cells did not increase aneuploidy. Insertion of STAG2 into nonexpressing cells led to reduced colony formation. Furthermore, analysis of bladder tumor tissue from more than 670 patients indicated that alterations in STAG2 were associated with a better prognosis.

"We found up to nine altered genes that had not been described before in this type of tumor, and of these we found that STAG2 was inactive in almost 40% of the least aggressive tumors," said senior author Dr. Francisco X. Real, head of the epithelial carcinogenesis group at the Spanish National Cancer Research Centre. "Some of these genes are involved in previously undescribed genetic pathways in bladder cancer, such as cell division and DNA repair; also, we confirmed and extended other genetic pathways that had previously been described in this cancer type, such as chromatin remodeling."

Related Links:

Spanish National Cancer Research Center

Print article



view channel

Molecular Light Shed on “Dark” Cellular Receptors

Scientists have created a new research tool to help find homes for orphan cell-surface receptors, toward better understanding of cell signaling, developing new therapeutics, and determining causes of drug side-effects. The approach may be broadly useful for discovering interactions of orphan receptors with endogenous, naturally... Read more

Lab Technologies

view channel
Image: The new ambr 15 fermentation micro-bioreactor system was designed to enhance microbial strain screening applications (Photo courtesy of Sartorius Stedim Biotech).

New Bioreactor System Streamlines Strain Screening and Culture

Biotechnology laboratories working with bacterial cultures will benefit from a new automated micro bioreactor system that was designed to enhance microbial strain screening processes. The Sartorius... Read more


view channel

Purchase of Biopharmaceutical Company Will Boost Development of Nitroxyl-Based Cardiovascular Disease Drugs

A major international biopharmaceutical company has announced the acquisition of a private biotech company that specializes in the development of drugs for treatment of cardiovascular disease. Bristol-Myers Squibb Co. (New York, NY, USA) has initiated the process to buy Cardioxyl Pharmaceuticals Inc. (Chapel Hill, NC, USA).... Read more
Copyright © 2000-2015 Globetech Media. All rights reserved.