Corporate Banner
Satellite Banner
Genomics
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

Join For Free

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 3,500+ scientific posters on ePosters
  • More than 5,000+ 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

Genetic Catalog Unprecedented Tool for Disease Diagnosis
Largest collection of human exome sequence data yields unprecedented tool for diagnosing rare disease.
Thursday, August 18, 2016
Broken Gene May Help Protect Against Ulcerative Colitis
Researchers have uncovered a protective genetic mutation that is specific to ulcerative colitis.
Friday, August 12, 2016
Shining A Light On Bladder Cancer
Researchers scrutinize patterns of mutations in bladder tumor genomes, gleaning insights into the roles of DNA repair and tobacco-related DNA damage.
Friday, May 06, 2016
Screen of Human Genome Reveals Set of Genes Essential for Cellular Viability
Using two complementary analytical approaches, scientists at Whitehead Institute and Broad Institute of MIT and Harvard have for the first time identified the universe of genes in the human genome essential for the survival and proliferation of human cell lines or cultured human cells.
Monday, October 19, 2015
DARPA Awards $32 Million Contract to MIT, Broad Institute Foundry
A facility at the Broad Institute of MIT and Harvard and MIT that aims to achieve the full potential of engineering biology has received a five-year, $32 million contract from the Defense Advanced Research Projects Agency (DARPA).
Monday, September 28, 2015
Scientists Discover New System For Human Genome Editing
CRISPR-Cpf1 system could disrupt both scientific and commercial landscape.
Monday, September 28, 2015
Broad Institute & Google Genomics Combine Bioinformatics and Computing Expertise
Both companies explore how to break down major technical barriers that increasingly hinder biomedical research.
Thursday, June 25, 2015
CRISP-Disp Leverages CRISPR-Cas9 to Deliver RNA Structures to Targets in the Genome
A team of researchers from the Broad Institute and the Harvard Stem Cell Institute has developed CRISP-Disp, a method that expands on the CRISPR-Cas9 system, allowing researchers to display multiple, large RNA structures on the Cas9 protein.
Wednesday, June 10, 2015
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
Single-cell Analysis Hits its Stride
Advances in technology and computational analysis enable scale and affordability, paving the way for translational studies.
Saturday, May 23, 2015
Highly Efficient New Cas9 for In Vivo Genome Editing
New finding is expected to expand therapeutic and experimental applications of CRISPR.
Tuesday, April 07, 2015
Broad Institute of MIT and Harvard and Bayer Healthcare Expand their Partnership
Collaboration to develop therapies for cardiovascular disease.
Thursday, April 02, 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
Scientists Map the Human Loop-ome, Revealing a New Form of Genetic Regulation
Researchers describe the results of a five-year effort to map, in unprecedented detail, how the 2-meter long human genome folds inside the nucleus of a cell.
Tuesday, December 23, 2014
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
Scientific News
Faecal Bacteria Linked to Body Fat
Researchers at King’s College London have found a new link between the diversity of bacteria in human poo – known as the human faecal microbiome - and levels of abdominal body fat.
Scientists Find Lethal Vulnerability in Treatment-Resistant Lung Cancer
The study describes how the drug Selinexor killed lung cancer cells and shrank tumors in mice when used against cancers driven by the aggressive and difficult-to-treat KRAS cancer gene.
How Baby’s Genes Influence Birth Weight And Later Life Disease
The large-scale study could help to target new ways of preventing and treating these diseases.
Modified Yeast Shows Plant Response to Key Hormone
Researchers have developed a toolkit based on modified yeast to determine plant responses to auxin.
ReadCoor Launched to Commercialize 3D Sequencing Tech
ReadCoor will leverage the Wyss Institute’s method for simultaneously sequencing and mapping RNAs within cells and tissues to advance development of diagnostics.
NCI Collaborates with Multiple Myeloma Research Foundation
NCI collaborates with MMRF to incorporate genomic and clinical data into NCI Genomic Data Commons database.
Epigenetic Clock Predicts Life Expectancy
New research finds 5 percent of population ages faster, faces shorter lifespan.
Regulatory RNA Essential to DNA Damage Response
Researchers discover a tumour suppressor is stabilized by an RNA molecule, which helps cells respond to DNA damage.
Death-or-Repair Switch Protein Identified
Researchers have identified a protein that plays a key role in the decision process of cell damage repair or cellular suicide.
Blood Pressure Drug May Boost Effectiveness of Lung Cancer Treatment
Researchers at Imperial College London have suggested that the blood pressure drug may make a type of lung cancer treatment more effective.
Skyscraper Banner

SELECTBIO Market Reports
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
3,500+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
5,000+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!