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

Pan-Cancer Studies Find Common Patterns Shared by Different Tumor Types

Published: Wednesday, October 02, 2013
Last Updated: Wednesday, October 02, 2013
Bookmark and Share
Findings may open up new treatment options by extending therapies effective in one cancer type to others with a similar genomic profile.

Cancer encompasses a complex group of diseases traditionally defined by where in the body it originates, as in lung cancer or colon cancer. This framework for studying and treating cancer has made sense for generations, but molecular analysis now shows that cancers of different organs have many shared features, while cancers from the same organ or tissue are often quite distinct.

The Pan-Cancer Initiative, a major effort to analyze the molecular aberrations in cancer cells across a range of tumor types, has yielded an abundance of new findings reported in 18 forthcoming papers, including four published in the October issue of Nature Genetics. The initiative, launched in October 2012 at a meeting in Santa Cruz, California, is part of the Cancer Genome Atlas (TCGA) project led by the National Cancer Institute and the National Human Genome Research Institute.

Josh Stuart, professor of biomolecular engineering at the University of California, Santa Cruz, helped organize the Pan-Cancer Initiative and is lead author of a commentary in Nature Genetics giving an overview of the project and its initial findings.

"For years we've been looking at one tumor type at a time, but there are patterns you can only spot by making connections across different tissues and tumor types. Finding these similarities across tissues can have important implications for treatment," Stuart said.

For example, some types of bladder cancer look very similar to certain lung and head-and-neck cancers, and recognizing those similarities may open up new therapeutic options. "This could allow oncologists to apply all they know about treating head-and-neck squamous cell tumors to the ten percent of bladder cancers that have the same characteristics," Stuart said.

TCGA is generating comprehensive maps of the key genomic changes in major types and subtypes of cancer, eventually covering at least 20 different cancer types. TCGA researchers are profiling thousands of tumors to discover molecular aberrations at the DNA, RNA, protein, and epigenetic levels. The Pan-Cancer Initiative has done comparative analyses of the first 12 tumor types profiled by TCGA.

The analyses show that the tissue of origin is an important factor, producing a dominant signal that groups tumors mostly according to their tissue of origin. But the data also reveal a number of interesting signals that cut across tumor types and suggest new ways of categorizing tumors, Stuart said. In addition, the statistical power gained by combining all of the data available from different tumor types has enabled researchers to see new patterns of genomic aberrations.

"In ovarian cancer, for example, we were able to identify mutations that correlate with the response to treatment, but only by using data from other types of cancer," Stuart said.

A persistent problem in cancer genomics has been distinguishing "driver" mutations from "passenger" mutations. Cancer cells often accumulate large numbers of genetic mutations that do not play a role in driving the uncontrolled cell growth that is a hallmark of cancer. These passenger mutations greatly complicate efforts to identify the genomic drivers of cancer. Aggregating data from the 12 tumor types gave Pan-Cancer researchers enough statistical power to see patterns that weren't apparent before. One of the forthcoming papers identifies with high confidence many new genomic drivers of cancer, Stuart said.

The Pan-Cancer analyses have also revealed the importance of new classes of mutations, such as those that affect how a cell's DNA is packaged in the chromosomes. As cells differentiate into specialized cell types during an organism's development, some genes are turned off and others are turned on depending on how the DNA is packaged together with specialized proteins to make "chromatin." Genomic changes (gene amplification, deletion or mutation) affecting genes that control the packaging of DNA can disrupt this key regulatory mechanism. One of the Nature Genetics papers (Zack et al.) analyzed amplifications and deletions and found 104 novel regions that had not been associated with cancer previously, and these regions contain a rich supply of genes involved in "epigenetic" modifications of chromatin.

"There are so many different ways to mess up the packaging of DNA that the mutations look random in any one tumor type, but now we have enough data to see that chromatin remodeling is a big factor in a lot of these tumors," Stuart said.

Stuart played a central role in creating the organizational framework that made the Pan-Cancer analyses possible. The project started as an informal collaboration among members of the TCGA research network, but then quickly expanded to include many other interested researchers. Coordinating all these efforts was a major task. Stuart worked with the bioinformatics company Sage Bionetworks to create a data repository called Synapse for the project. To ensure that everyone was working from the same data set, a data "freeze" was established in December 2012. But Stuart realized that many important analyses would depend on the results of other analyses carried out by different research groups.

"The interdependencies are so complicated that everybody had to abide by a schedule in order to play the game," Stuart said. "The system worked really well, and the project has ballooned because there are so many interesting things to look at. We have 18 papers coming out in this first release, and there are 60 more Pan-Cancer papers coming that I'm currently tracking."

The Synapse system created by Sage Bionetworks is described in one of the Nature Genetics papers (Omberg et al.). "This beautifully organized data repository is now available for scientists around the world to use to go beyond these initial analyses and discover even more about cancer," Stuart said.

Researchers will continue to use the framework and procedures Stuart established as they integrate new tumor types and new data from TCGA, as well as data from other cancer genomics projects. Stuart has just been named, along with Gad Getz of the Broad Institute of MIT and Harvard, to lead an international pan-cancer initiative that will combine TCGA data with data from other cancer genomics efforts around the world.

The hope is that these cross-tumor investigations will lead to new and improved cancer treatments. One goal is to identify biomarkers that can be used across a range of tumor types to indicate which therapies are likely to be most effective. The results of these studies may also point toward targets for novel therapeutic agents that can be tested clinically.

"These initial papers are just the first step, and we expect much more to come from the Pan-Cancer Initiative," Stuart said. "With the infrastructure now in place, we can scale up to look at more types of data, especially whole genome sequencing data, and to include many more tumor types, including rare tumors."


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

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.
Tuesday, July 28, 2015
Delivering Drugs to the Right Place
Thomas Weimbs has developed a targeted drug delivery method that could potentially slow the progression of polycystic kidney disease.
Monday, June 29, 2015
Designing New Pain Relief Drugs
Researchers have identified the molecular interactions that allow capsaicin to activate the body’s primary receptor for sensing heat and pain, paving the way for the design of more selective and effective drugs to relieve pain.
Thursday, June 11, 2015
Genetic Markers for Detecting and Treating Ovarian Cancer
Custom bioinformatics algorithm identifies human mRNAs that distinguish ovarian cancer cells from normal cells and provide new therapeutic targets
Wednesday, May 27, 2015
Using microRNA Fit to a T (Cell)
Researchers show B cells can deliver potentially therapeutic bits of modified RNA.
Friday, November 29, 2013
Digging Deeper Into Cancer
What a pathologist looks for in a Pap test sample, but hopes not to find, are oddly shaped cells with abnormally large nuclei. The same is true for prostate and lung cancer biopsies.
Tuesday, November 19, 2013
Nanotech Method Show Promise Against Pancreatic Cancer
Researchers at UCLA's Jonsson Comprehensive Cancer Center have developed a new technique for fighting deadly and hard-to-treat pancreatic cancer.
Monday, November 18, 2013
Researchers Un-Junking Junk DNA
A study shines a new light on molecular tools our cells use to govern regulated gene expression.
Wednesday, November 13, 2013
Powerful Anti-Cancer Compound Safely Delivered
Researchers have discovered a way to effectively deliver staurosporine (STS).
Tuesday, October 22, 2013
RNA Molecule Is Behind Behavior Changes Cued by Environment
UCSF study may point to key mechanism of cellular memory.
Thursday, September 05, 2013
Disabling Enzyme Cripples Tumors, Cancer Cells
Knocking out a single enzyme dramatically cripples the ability of aggressive cancer cells to spread and grow tumors.
Thursday, September 05, 2013
Scientists Devise Innovative Method to Profile and Predict the Behavior of Proteins
A class of proteins that are made up of multiple, interlocking molecular components, enzymes perform a variety of tasks inside each cell.
Friday, August 09, 2013
Non-Invasive Test Optimizes Colon Cancer Screening
Organized mailing campaigns could substantially increase colorectal cancer screening among uninsured patients.
Wednesday, August 07, 2013
Therapy Could Treat Breast Cancer that's Spread to Brain
Researchers have successfully combined cellular therapy and gene therapy in a mouse-model system to develop a viable treatment strategy for breast cancer that has spread to a patient's brain.
Tuesday, August 06, 2013
Major Changes Urged for Cancer Screening and Treatment
Scientific panel recommends new personalized strategies to reduce cancer overtreatment.
Tuesday, July 30, 2013
Scientific News
Long Telomeres Associated with Increased Lung Cancer Risk
Genetic predisposition for long telomeres predicts increased lung adenocarcinoma risk.
First Artificial Ribosome Designed
Researchers at the University of Illinois at Chicago and Northwestern University have engineered a tethered ribosome that works nearly as well as the authentic cellular component, or organelle, that produces all the proteins and enzymes within the cell.
Identifying a Key Growth Factor in Cell Proliferation
Researchers discover that aspartate is a limiter of cell proliferation.
A Gene-Sequence Swap Using CRISPR to Cure Haemophilia
For the first time chromosomal defects responsible for hemophilia have been corrected in patient-specific iPSCs using CRISPR-Cas9 nucleases
New Tool Uses 'Drug Spillover' to Match Cancer Patients with Treatments
Researchers have developed a new tool that improves the ability to match drugs to disease: the Kinase Addiction Ranker (KAR) predicts what genetics are truly driving the cancer in any population of cells and chooses the best "kinase inhibitor" to silence these dangerous genetic causes of disease.
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.
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!