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

Study Reveals Genomic Similarities Between Breast Cancer and Ovarian Cancers

Published: Tuesday, September 25, 2012
Last Updated: Tuesday, September 25, 2012
Bookmark and Share
The Cancer Genome Atlas, supported by NIH, finds shared genomic features that could aid treatments.

One subtype of breast cancer shares many genetic features with high-grade serous ovarian cancer, a cancer that is very difficult to treat, according to researchers supported by the National Institutes of Health.

The findings suggest that the two cancers are of similar molecular origin, which may facilitate the comparison of therapeutic data for subtypes of breast and ovarian cancers.

The researchers, using data generated as part of The Cancer Genome Atlas (TCGA), described new insights into the four standard molecular subtypes based on a comprehensive characterization of samples from 825 breast cancer patients.

The study, a collaborative effort funded by the National Cancer Institute (NCI) and the National Human Genome Research Institute (NHGRI), both part of NIH, was published online Sept. 23, 2012, and in print Oct. 4, 2012, in the journal Nature.

"TCGA's comprehensive characterization of their high-quality samples allows researchers an unprecedented look at these breast cancer subgroups," said NIH Director Francis S. Collins, M.D., Ph.D.

Analyses of genomic data have confirmed that there are four primary subtypes of breast cancer, each with its own biology and survival outlooks.

These TCGA findings are based on a large number of breast cancer specimens that capture a complete view of the genomic alterations.

The four groups are called intrinsic subtypes of breast cancer: HER2-enriched (HER2E), Luminal A (LumA), Luminal B (LumB) and Basal-like.

A fifth type, called Normal-like, was observed, but because of small numbers (only eight specimens) the researchers were unable to rigorously study it.

The TCGA Research Network uncovered marked genomic similarities between the Basal-like subtype and serous ovarian cancer.

The mutation spectrum, or types and frequencies of genomic mutations, were largely the same in both cancer types.

Further analyses identified several additional common genomic features, such as gene mutation frequency, suggesting that diverse genomic aberrations can converge into a limited number of cancer subtypes.

Computational analyses show that Basal-like breast cancer and serous ovarian cancer might both be susceptible to agents that inhibit blood vessel growth, cutting off the blood supply to the tumor, as well as to compounds that target DNA repair, which include chemotherapy drugs such as cisplatin.

The Basal-like subgroup has also been called Triple Negative Breast Cancer because many, though not all, Basal-like tumors are negative when tested for three receptors: the estrogen receptor, the progesterone receptor and human epidermal growth factor receptor 2 (HER2).

These receptors can trigger potent cell growth responses and act like a nametag, identifying the cell to the environment. The absence of these receptors means that treatments that target them will most likely be ineffective.

"The molecular similarity of one of the principal subtypes of breast cancer to that found in ovarian cancer gives us additional leverage to compare treatments and outcomes across these two cancers," noted Harold Varmus, M.D., NCI director. "This treasure trove of genetic information will need to be examined in great detail to identify how we can use it functionally and clinically."

According to the World Health Organization, there are approximately 1.3 million new cases of breast cancer and 450,000 deaths worldwide annually. Breast cancer is the most common cancer among women.

The majority of cases are sporadic, meaning there is not a family history of breast cancer, as opposed to genetic, where genes predispose a person to the disease. Men can also develop breast cancer, but it accounts for less than 1 percent of breast cancer cases.

Breast cancer tumors that have the HER2 receptor are called HER2-positive, and those that don't are called HER2-negative. When researchers analyzed the genomic findings from tumors determined to be HER2-positive by standard cellular tests, they found that only half of the samples could be characterized as belonging to the HER2E subtype.

The other half were characterized as Luminal subtypes, suggesting that there are at least two types of clinically defined HER2-positive tumors.

In general, the Luminal subtypes had the lowest overall mutation rate, but by contrast, had the largest number of genes observed to be significantly mutated. This suggests that each of the genes identified as significantly mutated in the Luminal subtypes is more likely to be important in fueling cancer progression.

The Luminal subtypes are characterized by the specific expression signature of multiple so-called transcription-factor genes, including ESR1, GATA3, FOXA1, XBP1 and cMYB. These genes have a complex interaction, cooperating in an orchestrated series of activations.

GATA3 and FOXA1 are frequently mutated, but those mutations are mutually exclusive, meaning that mutations were observed in either GATA3 or FOXA1 but never in both. However, ERS1 and XBP1 are highly expressed but infrequently mutated.

The scale of the TCGA program allows researchers to perform the integrative analyses that detect these complex patterns of genomic changes and interactions.

This close inspection of the cancer genome has led to a deeper understanding of the mutations essential for cancer progression, and several new candidates were identified in this study. The authors hope that discovery of these mutations will be a crucial step toward improving breast cancer therapies.

This publication focuses on the discoveries made through a combined analysis involving data from 825 breast cancer cases, which are freely available in the TCGA Data Portal, with several hundred more cases to come.

"The data generated by the TCGA program comprise a vast resource that investigators will be analyzing for years to come. The resource of information about breast cancer genomes will undoubtedly fuel myriad discoveries by the cancer research community," said Eric D. Green, M.D., Ph.D., NHGRI director.

So far, The Cancer Genome Atlas Research Network has published analyses on these cancers:

• glioblastoma multiforme (http://cancergenome.nih.gov/newsevents/newsannouncements/news_9_4_2008)
• ovarian serous adenocarcinoma (http://cancergenome.nih.gov/newsevents/newsannouncements/ovarianpaper)
• colorectal adenocarcinoma (http://www.cancer.gov/newscenter/pressreleases/2012/TCGAcolorectal)
• lung squamous cell carcinoma (http://www.cancer.gov/newscenter/newsfromnci/2012/LungSquamousTCGA)


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

The Genetics of Blood Pressure
Researchers have identifed areas of the genome associated with blood-pressure including 17 previously unknown loci.
Wednesday, September 21, 2016
Catalogue of Human Genetic Diversity Expands
The largest data set of human exomes to date has been assembled to better study seqence variants and their consequences.
Wednesday, September 07, 2016
$12.4M Awarded to Neural Regeneration Projects
The National Institutes of Health will fund six projects to identify biological factors that influence neural regeneration.
Friday, September 02, 2016
New Inflammatory Disease Discovered
NIH researchers have discovered a rare and potentially deadly disease - otulipenia - the mostly affects children.
Tuesday, August 23, 2016
Public Support for National Study
Survey shows the majority of respondents support or show willingness for national precision medicine study.
Thursday, August 18, 2016
Schizophrenia, Autism Share Genetic Causes
Monkey brain developmental atlas pinpoints when, where genes activate.
Tuesday, August 16, 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
Mutations Linked to Immunotherapy Resistance
Researchers uncover mutations in tumors of three patients with advanced melanoma that allowed the tumors to become resistant to the immune checkpoint inhibitor pembrolizumab (Keytruda®).
Tuesday, August 09, 2016
Genetic Cause of Rare Pediatric Neuropathy Identified
NIH mouse study identifies the mechanism responsible for a rare form of pediatric neuropathy.
Thursday, August 04, 2016
Depression Genetics Insight from Crowd-Sourced Data
Genome sites liked to depression have been discovered from data shared by people who had purchased their genetic profiles online.
Tuesday, August 02, 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
NIH Funds Million-Person Medicine Study
NIH announces $55million in awards to build foundations for ambitious Cohort Program that aims to engage 1 million participants in lifestyle, environments and genetics research.
Friday, July 08, 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
Significant Expansion Of Data Available In The Genomic Data Commons
Cancer genomic profile information from 18,000 adult cancer patients will be added to the database.
Wednesday, June 29, 2016
Predicting Effective Drug Combinations For TB
Researchers analyzed gene regulatory networks to explain the effectiveness of an experimental drug combination against drug-resistant tuberculosis bacteria.
Wednesday, June 15, 2016
Scientific News
A Diversity of Genomes
New DNA from understudied groups reveals modern genetic variation, ancient population shifts.
Gene Could Reduce Female Mosquitoes
Virginia Tech researchers have found a gene that can reduce female mosquitoes over many generations.
Improving Crop Efficiency with CRISPR
New study of CRISPR-Cas9 technology from Virginia Tech shows potential to improve crop efficiency.
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.
Bacteria Use Ranking Strategy to Fight Off Viruses
Researchers have explained why microbes store virus confrontation information sequentially, with most recent attacks first.
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
The Genetics of Blood Pressure
Researchers have identifed areas of the genome associated with blood-pressure including 17 previously unknown loci.
Mosquito Genetics Determine Tastes
Study reveals mosuito's preference for human versus animal biting is determined by genetics.
Quadruple Helix DNA Aids Cancer Therapies
Researchers have identified the role that a four-stranded version of DNA may play in the role of cancer progression.
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!