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

Study Establishes Basis for Genomic Classification of Endometrial Cancers

Published: Thursday, May 02, 2013
Last Updated: Thursday, May 02, 2013
Bookmark and Share
Proper categorization is important for choosing the best treatment.

A comprehensive genomic analysis of nearly 400 endometrial tumors suggests that certain molecular characteristics – such as the frequency of mutations -- could complement current pathology methods and help distinguish between principal types of endometrial tumors, as well as provide insights into potential treatment strategies.  In addition, the study, led by investigators in The Cancer Genome Atlas (TCGA) Research Network, revealed four novel tumor subtypes, while also identifying genomic similarities between endometrial and other types of cancers, including breast, ovarian, and colorectal cancers.

These findings represent the most comprehensive characterization of the molecular alterations in endometrial cancers available to date. They were published May 2, 2013, in the journal Nature. TCGA is funded and managed by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI), both part of the National Institutes of Health.

“With this latest study in a series of 20 planned TCGA tumor type characterizations, more genomic similarities are emerging between disparate tumor types,” said NIH Director Francis S. Collins, M.D., Ph.D.  “Teasing out heretofore unknown genomic markers or mutations in various cancers is again proving the value of TCGA.”

Clinically, endometrial cancers fall into two categories: endometrioid (type I) and serous (type II) tumors. Type I is correlated with excess estrogen, obesity, and a favorable prognosis, while type II is more common in older women and generally has a less favorable outcome. Type I tumors are often treated with radiation therapy, which helps stop or slow cancer growth, given in addition to or after the primary treatment. Type II tumors are generally treated with chemotherapy, in which drugs are used to kill the cancer cells or stop them from growing.

Distinguishing between different types of endometrial cancers is currently based on histology, an examination of a thin slice of tissue under a microscope. But categorizing endometrial cancer tissues is often difficult, and specialists frequently disagree on the classification of individual cases.

In this study, investigators showed that approximately 25 percent of tumors that pathologists classified as high-grade endometrioid showed frequent mutations in TP53, a tumor suppressor gene, as well as extensive copy number alterations, a term for when a cell has too many or too few copies of a genomic segment. Both are key molecular characteristics associated with serous tumors, along with a small number of DNA methylation changes, which are additions of a basic chemical unit to pieces of DNA. Most endometrioid tumors, by contrast, have few copy number alterations or mutations in TP53, though there are  frequent mutations in other well known cancer-associated genes, including PTEN, another tumor suppressor gene, and KRAS, a gene involved in regulating cell division.

These data suggest that some high grade endometrioid tumors have developed a strikingly similar pattern of alterations to serous tumors, and may benefit from a similar course of treatment.

“This study highlights the fact that some tumors with the same characterization by pathologists may have very different molecular features. That’s where these findings will be directly implemented in additional research, and also in the context of clinical trials,” said Douglas A. Levine, M.D., head of the Gynecology Research Laboratory at Memorial Sloan-Kettering Cancer Center, New York, and a co-leader in the study.

According to the authors, the new findings provide a roadmap for future clinical trials for endometrial cancer.  “Each tumor subtype might warrant dedicated clinical trials because of the marked genomic differences between them that are indicative of different drivers of cancer,” said study co-leader Elaine Mardis, Ph.D., co-director of the Genome Institute at Washington University School of Medicine, St. Louis.  “Developing therapies for each subtype independent of the other may improve outcomes, as has been shown in breast cancer.”

Investigators also found genomic similarities between endometrial cancers and other tumor types.  Previous TCGA research showed that a form of ovarian cancer (high-grade serous ovarian carcinoma) and a subtype of breast cancer (basal-like breast cancer) share many genomic features. In this study, the scientists found that endometrial serous carcinoma also has some of these same genomic characteristics. The cancers share a high frequency of mutations in TP53 (between 84 and 96 percent) and a low frequency in PTEN, with only 1 to 2 percent mutated. Surprisingly, the researchers also found many shared characteristics between endometrioid tumors and colorectal tumors. Both cancer types demonstrate a high frequency of microsatellite instability, where the repair mechanism for DNA is broken, and mutations in POLE, a gene responsible for producing a protein involved in DNA replication and repair. These genomic changes led to high mutation rates in both tumor types.

“TCGA’s multidimensional approach to collecting genomic data, including clinical and pathology information, have made these findings possible,” said Harold Varmus, M.D., NCI director. “Without the integrated characterization of so many tumor samples, correlations between histology and genomic data may not have been observed or potential clinical outcomes identified.”

With a complete analysis of the study’s findings, investigators have identified four novel genomic-based subtypes of endometrial cancer, which may set the stage for new diagnostic and treatment approaches. Each of the four genomic subtypes clustered together and was named for one of its notable characteristics:

-- The POLE ultramutated group was named for its unusually high mutation rates and hotspot mutations (sequences highly susceptible to mutation) in the POLE gene.
-- The hypermutated microsatellite instability group exhibited a high mutation rate, as well as few copy number alterations, but did not carry mutations in the POLE gene.
-- The copy number low group showed the greatest microsatellite stability but a high frequency of mutations in CTNNB1, a gene critical for maintaining the linings of organs, such as the endometrium.
-- The copy number high subtype was composed of mostly serous tumors, but included some endometrioid samples. This subtype displayed copy number alterations and a mutation landscape that was characteristic of serous tumors.

Endometrial cancer is the fourth most commonly diagnosed cancer among women in the United States. NCI estimates that close to 50,000 women will be diagnosed with endometrial cancer in 2013, with more than an estimated 8,000 deaths from the disease.

For a majority of patients diagnosed with aggressive, high grade tumors with metastases, the five-year survival rate is about 16 percent, though chemotherapy has been associated with an improvement in survival, and new targeted agents are being tested.

“Finding genomic similarities among types of breast, ovarian, endometrial and colorectal tumors once again reveals that cancer, although very complex, may have themes extending beyond tissue type that can be exploited for therapeutic benefit,” said Eric D. Green, M.D., Ph.D., NHGRI director. “These similar genomic features demonstrate hitherto unknown commonalities among these cancers.

To date, the TCGA Research Network has generated data and published analyses on glioblastoma multiforme, ovarian serous adenocarcinoma, colorectal adenocarcinoma, lung squamous cell carcinoma and invasive breast cancer. Data generated by TCGA are freely available at the TCGA Data Portal and CGHub.


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

Developing Novel Ear Infection Treatments
Research team engineers antibiotic gel for treating middle ear infections.
Wednesday, September 28, 2016
How Breast Cancers Resist Chemotherapy
Researchers discovered an unexpected way that breast cancers cells with mutant BRCA1 or BRCA2 genes acquire drug resistance and evade chemotherapies.
Wednesday, August 10, 2016
Researchers Develop Software That Could Facilitate Drug Development
AptaTRACE can identify aptamers, potentially speed drug advancement.
Saturday, July 30, 2016
Uncovering a New Principle in Chemotherapy Resistance in Breast Cancer
The NIH study has revealed an entirely unexpected process for acquiring drug resistance that bypasses the need to re-establish DNA damage repair in breast cancers that have mutant BRCA1 or BRCA2 genes.
Thursday, July 21, 2016
Largest-Ever Study of Breast Cancer Genetics in Black Women
The study will identify genetic factors that may underlie breast cancer disparities.
Thursday, July 07, 2016
Submissions Open for the Cancer Moonshot Program
NCI opens online platform to submit ideas about research for Cancer Moonshot.
Tuesday, April 19, 2016
Researchers Find Link Between Death of Tumor-Support Cells and Cancer Metastasis
Researchers at NIH have found that the lifespan of supportive cells in a tumor may control the spread of cancer.
Tuesday, February 23, 2016
Cancer Drug Target Visualized at Atomic Resolution
New study using cryo-electron microscopy shows how potential drugs could inhibit cancer.
Thursday, February 04, 2016
Scientists Develop Genetic Blueprint of Inner Ear Cell Development
Two studies in mice use new technique to provide insight into cell development critical for hearing, balance.
Saturday, October 17, 2015
NIH Breast Cancer Research to Focus On Prevention
A new phase of the Breast Cancer and the Environment Research Program (BCERP), focused on prevention, is being launched at the National Institutes of Health.
Friday, October 09, 2015
New Gene Therapy for Vision Loss From a Mitochondrial Disease
NIH-funded study shows success in targeting mitochondrial DNA in mice.
Tuesday, October 06, 2015
Cellular Factors that Shape the 3D Landscape of the Genome Identified
Researchers have identified 50 cellular factors required for the proper 3D positioning of genes by using novel large-scale imaging technology.
Tuesday, August 18, 2015
Tell-tale Biomarker Detects Early Breast Cancer in NIH-funded Study
The study published online in the issue of Nature Communications.
Thursday, August 13, 2015
Study Shows Promise of Precision Medicine for Most Common Type of Lymphoma
The study appeared online July 20, 2015, in Nature Medicine.
Tuesday, July 21, 2015
Potential Therapeutic for Blinding Eye Disease
NIH research points to microglia as potential therapeutic target in retinitis pigmentosa.
Thursday, July 02, 2015
Scientific News
Developing Novel Ear Infection Treatments
Research team engineers antibiotic gel for treating middle ear infections.
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.
Wearable Microscope Can Measure Fluorescent Dyes Through Skin
UCLA research could make monitoring disease biomarkers easier and more cost-effective.
Potential of New Insect Control Traits in Agriculture
Researchers have discovered a protein that shows promise as an alternate corn rootworm control mechanism.
Fighting Cancer with Sticky Nanoparticles
Treatment that uses bioadhesive nanoparticles drug carriers proved more effective than conventional treatments for certain cancers.
Fighting Plant Pathogens with RNA
Researchers develop strategy that could lead to environmentally friendly fungicide to fight pathogens.
Smart Material Hunts Cancers
Team has created smart material that locates and images cancer or tumour sites in tissue.
Gene Therapy Technique May Help Prevent Cancer Metastasis
Gene-regulating RNA molecules could help treat early-stage breast cancer tumors before they spread.
Enhancing Antibiotics to Defeat Resistant Bacteria
Scientists enhance ability of antibiotics to defeat resistant types of bacteria using molecules called PPMOs
Examining mtDNA May Help Identify Unknown Ancestry That Influences Breast Cancer Risk
Researchers studying mtDNA in a group of triple negative breast cancer patients found that 13 percent of participants were unaware of ancestry that could influence their risk of cancer.
SELECTBIO

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!