Corporate Banner
Satellite Banner
RNAi
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Endometrial Cancer Findings Emerge from Genome Sequencing Study

Published: Friday, May 10, 2013
Last Updated: Friday, May 10, 2013
Bookmark and Share
Novel tumor sub-types have been identified that could lead to better risk stratification and more individualized and targeted treatments.

Investigators from The Cancer Genome Atlas (TCGA) Research Network, including several scientists from the Broad Institute, have published the most comprehensive genomic analysis of endometrial cancer to date. Their study, which appeared in the May 2 issue of Nature, classified the tumors into four novel sub-types and identified molecular similarities between some of these sub-types and other forms of cancer, including ovarian, breast, and colorectal cancers. The findings provide new clues about the molecular pathways that may contribute to the disease, and could help identify which patients might benefit from aggressive treatment.

“This paper provides the most refined picture to date of the genetic causes of endometrial cancer. This picture enables us to identify biological pathways that lead to endometrial cancer as well as possible therapeutic targets and approaches to treatment,” explained paper co-author Rameen Beroukhim. Beroukhim is an associate member in the Broad’s Cancer Program, as well as an assistant professor at Dana-Farber Cancer Institute and Harvard Medical School, and an attending physician at Brigham and Women’s Hospital.

Endometrial cancer, which forms in the lining of the uterus, is the fourth most common cancer diagnosed in women, with nearly 50,000 cases diagnosed last year in the U.S. alone. While it can be deadly, most women with endometrial cancer die of other causes without having shown signs of the disease. However, determining which women are at high risk can be difficult.

Endometrial cancers are classified into two types: endometrioid, a less severe form associated with excess estrogen and obesity, and serous, a more life-threatening form that tends to afflict older women. The type of endometrial cancer a patient has is currently determined through histology, in which a small slice of the tumor is examined under a microscope. That diagnosis dictates what type of treatment a patient receives. Unfortunately, histology can be imprecise, and many patients suspected of having serous tumors endure aggressive treatments that may not be necessary.

“We know that the long-term side-effects of treatment are extensive for many of these patients. What we need are molecular markers that can classify patients as high-risk for recurrence and death, and low-risk for death so that we can avoid over-treatment,” said co-author Helga Salvesen, a clinician and endometrial cancer specialist. Salvesen is a visiting scientist at the Broad and professor at the University of Bergen, Norway.

The TCGA study identified molecular profiles in endometrial cancer that may make risk assessment easier. The researchers analyzed the genomes of nearly 400 endometrial tumors, and found patterns in the genetic data that enabled them to classify endometrial cancers into four novel sub-types.

One of these sub-types was found to have frequent mutations in the tumor suppressor gene TP53, as well as extensive copy number variations throughout the genome. Copy number variations occur when parts of a person’s DNA are either lost or amplified, resulting in an abnormal number of copies of the affected genes. Serous tumors fell into this sub-type, as did roughly 25% of endometrioid tumors. These endometrioid tumors tended to be “high-grade” endometrioid tumors that were associated with unfavorable prognoses.

The identification of this more severe sub-type of serous and serous-like endometrioid tumors could help clinicians determine which patients should receive aggressive treatment.

“What we’ve found is that there are some tumors that would be classified as endometrioid based on histology that in fact look molecularly like serous cancers,” said Andrew Cherniack, a research scientist in the Broad TCGA Genome Characterization Center who led the copy number analysis for the study and was responsible for some of the paper’s key findings. “Pending further studies, this molecular classification could provide a better tool for pathologists than histology alone to determine which tumors put patients at high-risk.”

The study also revealed that some endometrial cancers share genomic characteristics with other forms of cancer. Serous tumors and endometrioid tumors with serous-like profiles look molecularly similar to ovarian serous cancer and basal-like breast cancer. All three cancers possess similar copy number variations, as well as a high rate of mutations in TP53. They also share a low mutation rate in another tumor suppressor gene called PTEN, which is frequently associated with endometrial cancer.

The researchers also found similarities between certain endometrioid cancers and colorectal cancer. These cancers share a mutation in POLE, a gene involved in DNA repair. That mutation impairs the mechanism involved in replicating DNA, resulting in a far higher mutation rate than is seen in other types of cancer.

Both of the paper’s key findings – the molecular classification of novel sub-types of endometrial cancer, and the identification of genomic similarities between endometrial cancers and other forms of cancer – suggest the need for a new model for clinical trials for this disease. Traditionally, endometrial cancers have been grouped together when treatments have been tested. The TCGA study suggests that, when assessing potential treatments, it may be more effective instead to group endometrial cancers based on their molecular profiles. Not only might this division facilitate the discovery of effective, targeted treatments, but drugs found to work against one type of cancer (be it endometrial, ovarian, or breast cancer) may also be found to fight other cancer types that share similar molecular underpinnings.

TCGA is a multi-institutional effort funded by the National Cancer Institute and National Human Genome Research Institute, which are both part of the National Institutes of Health. The Broad Institute serves as a data generation and analysis center for TCGA. These activities are led by several Broad scientists, including Matthew Meyerson and Stacey Gabriel, who head the Broad TCGA Genome Characterization Center, and Gad Getz, principal investigator of the Broad TCGA Genome Data Analysis Center.

TCGA has published analyses of seven cancer genomes to date, including this study of endometrial cancer and a study of acute myelogenous leukemia, which was also published on May 2, in the New England Journal of Medicine. TCGA intends to characterize at least 20 cancer genomes, and to continue to make all of the data freely available to the cancer research community.

The researchers wish to thank the many donors who contribute the specimens and clinical data that make these studies possible.


Further Information
Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 2,400+ scientific posters on ePosters
  • More than 3,700+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

GTEx: Useful Expression For Cancer Research
GTEx Project has recently published several papers reporting on findings from its two-year pilot phase.
Tuesday, May 26, 2015
In vivo CRISPR-Cas9 Screen Sheds Light On Cancer Metastasis And Tumor Evolution
Genome-scale study points to drivers of tumor evolution and metastasis, provides roadmap for future in vivo Cas9 screens.
Friday, March 06, 2015
Disorder in Gene-Control System is a Defining Characteristic of Cancer, Study Finds
Findings indicate that the disarray in the on-off mechanism is one of the defining characteristics of cancer.
Tuesday, December 23, 2014
Two Studies Identify A Detectable, Pre-Cancerous State In The Blood
Findings pave way for new lines of cancer research focused on detection and prevention.
Thursday, November 27, 2014
Dramatic Response And Resistance To Cancer Drug Traced
Sequencing reveals why thyroid tumor responded to, and eventually resisted, treatment.
Friday, October 10, 2014
Study Expands the Cancer Genomics Universe
The universe of cancer mutations is much bigger than previously thought, and key cancer genes are still to be discovered.
Tuesday, January 28, 2014
Predicting Cancer’s Next Move
Research offers a new approach to studying drug resistance in cancer.
Monday, November 11, 2013
Study Finds Rules for Cancer Drivers
Any number of alterations to an individual’s genetic code has the potential to make a cell malfunction and proliferate into cancer tumors.
Monday, September 30, 2013
Broad Institute and Bayer Join Forces
The Broad Institute has entered into a strategic alliance with Bayer Healthcare in the area of oncogenomics and drug discovery.
Wednesday, September 11, 2013
Bringing Out the Usual – and Unusual – Cancer Genomics Suspects
Several years ago, researchers sequencing lung cancer genomes encountered a number of red herrings.
Tuesday, June 18, 2013
Chemical Screen Points to New Line of Attack Against Neuroblastoma
In the war on neuroblastoma, the current chemical weaponry is reaching its limit.
Monday, June 10, 2013
ATARiS Informatics Platform Hits the Jackpot
ATARiS is one of several tools developed at the Broad Institute to precisely tune in to the signals within noisy datasets.
Wednesday, May 22, 2013
Researchers Unearth New Clues About How Prostate Cancer Evolved
With the help of a computational model, Broad researchers were able to reconstruct the genomes of prostate cancer cells.
Thursday, May 16, 2013
Delivering on a Promise: Nanoparticles Carry siRNA to Tumours
RNA interference, a gene-silencing phenomenon discovered in the late 1990s, was hailed for its potential as a treatment in cancer and other diseases.
Friday, September 21, 2012
New Potential Targets Discovered for Treating Squamous Cell Lung Cancers
The Cancer Genome Atlas finds important genomic alterations in second most common lung cancer type.
Monday, September 10, 2012
Scientific News
RNAi Screening Trends
Understand current trends and learn which application areas are expected to gain in popularity over the next few years.
New Material Opens Possibilities for Super-Long-Acting Pills
A pH-responsive polymer gel could create swallow able devices, including capsules for ultra-long drug delivery.
New Tool For Investigating RNA Gone Awry
A new technology – called “Sticky-flares” – developed by nanomedicine experts at Northwestern University offers the first real-time method to track and observe the dynamics of RNA distribution as it is transported inside living cells.
Access Denied: Leukemia Thwarted by Cutting Off Link to Environmental Support
A new study reveals a protein’s critical – and previously unknown -- role in the development and progression of acute myeloid leukemia (AML), a fast-growing and extremely difficult-to-treat blood cancer.
New Weapon in the Fight Against Blood Cancer
This strategy, which uses patients’ own immune cells, genetically engineered to target tumors, has shown significant success against multiple myeloma, a cancer of the plasma cells that is largely incurable.
TOPLESS Plants Provide Clues to Human Molecular Interactions
Scientists at Van Andel Research Institute have revealed an important molecular mechanism in plants that has significant similarities to certain signaling mechanisms in humans, which are closely linked to early embryonic development and to diseases such as cancer.
Toxin from Salmonid Fish has Potential to Treat Cancer
Researchers from the University of Freiburg decode molecular mechanism of fish pathogen.
Scientists Create CRISPR/Cas9 Knock-In Mutations in Human T Cells
In a project spearheaded by investigators at UC San Francisco, scientists have devised a new strategy to precisely modify human T cells using the genome-editing system known as CRISPR/Cas9.
Long-sought Discovery Fills in Missing Details of Cell 'Switchboard'
A biomedical breakthrough reveals never-before-seen details of the human body’s cellular switchboard that regulates sensory and hormonal responses.
Tracking Breast Cancer Before it Grows
A team of scientists led by University of Saskatchewan researcher Saroj Kumar is using cutting-edge Canadian Light Source techniques to screen and treat breast cancer at its earliest changes.
SELECTBIO

Skyscraper Banner
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
2,400+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
3,700+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FREE!