Corporate Banner
Satellite Banner
Scientific Communities
Become a Member | Sign in
Home>News>This Article

Researchers Unearth New Clues About How Prostate Cancer Evolved

Published: Thursday, May 16, 2013
Last Updated: Thursday, May 16, 2013
Bookmark and Share
With the help of a computational model, Broad researchers were able to reconstruct the genomes of prostate cancer cells.

Imagine you’re visiting the Acropolis. You tour the ruins, taking snapshots as you go. Later, at home, you tell your family and friends about your visit and someone, noticing the building’s advanced deterioration, asks: well, how did it get that way? Now, say you knew nothing about the Acropolis, and could only rely on your photos and memory to describe the place. What would you say? Without the rich archeological history of the Acropolis, you’d be missing a huge part of the story.

Now imagine a cancer cell as a similar kind of ruin. Over time mutations accumulate, pushing the cell further and further from its original shape and function, eventually overwhelming its ability to control growth. When scientists sequence a cancer genome, the resulting data is essentially a snapshot of the tumor and its mutations at the time it was sampled. But what stories would emerge if we knew the order in which those mutations occurred?

In the case of prostate cancer — the second most lethal cancer in American men — research has demonstrated that structural genomic alterations, such as broken and rearranged chromosomes, are key to tumor development and progression. With no evidence to suggest a chronology for these breaks and repairs, researchers generally assumed that they accumulated gradually over time, often as a result of cell division. But new research is suggesting the deterioration isn’t gradual at all.

For the first time, a team of scientists from the Broad, Dana-Farber Cancer Institute, and Weill Cornell Medical Center has revealed the “cellular archeology” of prostate cancer cells. Using a computational model, the team was able to track how mutations accumulated in the genomes of 55 prostate cancer tumors. The results of the study, recently published in Cell, revealed that mutations often occur in abrupt, interconnected bursts, resulting in large-scale rearrangement of DNA.

“We’ve known for a long time that the rearrangement of certain chromosomes is key to the development of prostate cancer and we suspected they were the result of some very complex DNA-damaging events,” says Sylvan Baca, the study’s first author and cellular Indiana Jones. As a researcher in Broad senior associate member Levi Garraway’s lab and part of the Broad/Dana-Farber/Weill Cornell team, Baca had observed how the genomes of prostate cancer cells appeared as if they’d been taken apart and put back together the wrong way. In an attempt to fill in the gaps in the story, Baca developed ChainFinder — a modeling algorithm that was able to reconstruct the shattered genomes and determine the chronology of the alterations.

“Interestingly, our findings indicate that many of these rearrangements arise in a highly interdependent fashion, and may often occur together within a single cell,” said Baca, who along with the other members of the team, dubbed these damaging events “chromoplexy” from the Greek word to interweave or integrate. Similar to the idea of punctuated evolution in the population sciences — which suggests that that major genetic changes can happen to select populations in a relatively small window of time — chromoplexy indicates that sets of mutations may originate together, drastically altering cells.

“While we can’t yet say much about the timing of the events, or what the events are, the study suggests that just a few of these events may be enough to lead to the changes we know result in prostate cancer,” says Baca. A major goal of prostate cancer research is to identify new drug targets, as well as genetic characteristics that could distinguish aggressive forms of the disease. While researchers are currently working to further understand the initiating source of these events, Baca speculates that in the future profiling cells for chromoplexy may be a way to identify certain “linchpin” mutations in particular cancers.

The idea that periodic bursts of genetic upheaval, resulting in a cascade of changes eventually leading to tumor growth, has been hinted at in other cancers — but the identification of chromoplexy suggests this sort of genomic derangement may be far more common than previously thought.

“The complex genomic restructuring we discovered is a unique and important model of carcinogenesis which likely has relevance for other tumor types,” said Garraway, a co-senior author of the study. The team is now using ChainFinder to study other cancers known for containing complex genetic rearrangements, including lung adenocarcinoma, melanoma, and breast cancer, to see if those changes are also the result of chromoplexy.

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 2,800+ scientific posters on ePosters
  • More Than 4,000+ 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 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

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
Diagnostics Breakthrough Brings Viral Sequencing to Doctors’ Toolkit
New screening tool produces up to 10,000-fold improvement in viral matches compared with traditional high-throughput methods.
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
Researchers Develop a New Means of Killing Harmful Bacteria
Engineered particles are capable of producing toxins that are deadly to targeted bacteria.
Friday, June 26, 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
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
Scientific News
High Throughput Mass Spectrometry-Based Screening Assay Trends
Dr John Comley provides an insight into HT MS-based screening with a focus on future user requirements and preferences.
How a Genetic Locus Protects Adult Blood-Forming Stem Cells
Mammalian imprinted Gtl2 protects adult hematopoietic stem cells by restricting metabolic activity in the cells' mitochondria.
Genetic Basis of Fatal Flu Side Effect Discovered
A group of people with fatal H1N1 flu died after their viral infections triggered a deadly hyperinflammatory disorder in susceptible individuals with gene mutations linked to the overactive immune response, according to a recent study.
New Tech Vastly Improves CRISPR/Cas9 Accuracy
A new CRISPR/Cas9 technology developed by scientists at UMass Medical School is precise enough to surgically edit DNA at nearly any genomic location, while avoiding potentially harmful off-target changes typically seen in standard CRISPR gene editing techniques.
The MaxSignal Colistin ELISA Test Kit from Bioo Scientific
Kit can help prevent the antibiotic apocalypse by keeping last resort drugs out of the food supply.
"Good" Mozzie Virus Might Hold Key to Fighting Human Disease
Australian scientists have discovered a new virus carried by one of the country’s most common pest mosquitoes.
Non-Disease Proteins Kill Brain Cells
Scientists at the forefront of cutting-edge research into neurodegenerative diseases such as Alzheimer’s and Parkinson’s have shown that the mere presence of protein aggregates may be as important as their form and identity in inducing cell death in brain tissue.
Closing the Loop on an HIV Escape Mechanism
Research team finds that protein motions regulate virus infectivity.
New Class of RNA Tumor Suppressors Identified
Two short, “housekeeping” RNA molecules block cancer growth by binding to an important cancer-associated protein called KRAS. More than a quarter of all human cancers are missing these RNAs.
Potential Treatment for Life-Threatening Viral Infections Revealed
The findings point to new therapies for Dengue, West Nile and Ebola.
Scroll Up
Scroll Down
Skyscraper Banner

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
2,800+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,000+ scientific videos