Genomic study shows colon and rectal tumors constitute a single type of cancer

July 18, 2012
This image shows translocations involving chromosome 1 in a set of colon and rectal samples. The locations of the breakpoints leading to the translocation and circular representations of all rearrangements in tumors with a fusion are shown. The red line lines represent fusions, black lines indicate other rearrangements. Credit: The Cancer Genome Atlas (TCGA), National Cancer Institute

The pattern of genomic alterations in colon and rectal tissues is the same regardless of anatomic location or origin within the colon or the rectum, leading researchers to conclude that these two cancer types can be grouped as one, according to The Cancer Genome Atlas (TCGA) project's large-scale study of colon and rectal cancer tissue specimens.

In multiple types of genomic analyses, colon and results were nearly indistinguishable. Initially, the TCGA Research Network studied as distinct from rectal tumors.

"This finding of the true genetic nature of colon and rectal cancers is an important achievement in our quest to understand the foundations of this disease," said NIH Director Francis S. Collins, M.D., Ph.D. "The data and knowledge gained here have the potential to change the way we diagnose and treat certain cancers."

The study also found several of the recurrent that contribute to colorectal cancer. The study, funded by the (NCI) and the National Institute (NHGRI), both parts of the National Institutes of Health, was published online in the July 19, 2012, issue of the journal Nature.

There is a known negative association between aggressiveness of colorectal tumors and the phenomenon of hypermutation, in which the rate of genetic mutation is abnormally high because normal are disrupted. In this study, 16 percent of the specimens were found to be hypermutated. Three-fourths of these cases exhibited microsatellite instability (MSI), which often is an indicator for better prognosis. Microsatellites are repetitive sections of DNA in the genome. If mutations occur in the genes responsible for maintaining those regions of the genome, the microsatellites may become longer or shorter; this is called MSI.

NCI estimates that more than 143,000 people in the United States will be diagnosed with colorectal cancer and that 51,500 are likely to die from the disease in 2012. Colorectal cancer is the fourth most common cancer in men, after non-melanoma skin, prostate and lung cancer. It is also the fourth most common cancer in women, after non-melanoma skin, breast and lung cancer.

The researchers observed that in the 224 colorectal cancer specimens examined, 24 genes were mutated in a significant numbers of cases. In addition to genes found through prior research efforts (e.g., APC, ARID1A, FAM123B/WTX, TP53, SMAD4, PIK3CA and KRAS), the scientists identified other genes (ARID1A, SOX9 and FAM123B/WTX) as potential drivers of this cancer when mutated. It is only through a study of this scale that these three genes could be implicated in this disease.

"While it may take years to translate this foundational genetic data on colorectal cancers into new therapeutic strategies and surveillance methods, this genetic information unquestionably will be the springboard for determining what will be useful clinically against colorectal cancers,'' said Harold E. Varmus, M.D., NCI director.

The research network also identified the genes ERBB2 and IGF2 as mutated or overexpressed in colorectal cancer and as potential drug targets. These genes are involved in regulating cell proliferation and were observed to be frequently overexpressed in colorectal tumors. This finding points to a potential drug therapy strategy in which inhibition of the products of these genes would slow progression of the cancer.

A key part of this study was the analysis of signaling pathways. Signaling pathways control gene activity during cell development and regulate the interactions between cells as they form organs or tissues. Among other findings, the TCGA Research Network identified new mutations in a particular signaling cascade called the WNT pathway. According to the researchers, this finding will improve development of WNT signaling inhibitors, which show initial promise as a class of drugs that could benefit colorectal cancer patients.

In addition to examining the WNT pathway, the investigators also identified RTK/RAS and AKT-PI3K as pathways that are altered in a substantial set of colorectal tumors, which may show promise for targeting therapies for colorectal . Because of these findings, drug developers may now be able to narrow their scope of investigation with an expectation of producing more focused therapeutic approaches, noted the researchers.

"It takes a critical group of researchers to conduct research at this scale and of this quality," said Eric. D. Green, M.D., Ph.D., NHGRI director. "This study is among the most comprehensive of its kind to date and vividly illustrates how TCGA data sets can shed new light on fundamental properties of human cancers."

Explore further: New class of cancer drugs could work in colon cancers with genetic mutation, study finds

More information: TCGA Research Network. Comprehensive Molecular Characterization of Human Colon and Rectal Tumors. July 19, 2012. Nature. DOI: 10.1038/nature11252

Related Stories

New class of cancer drugs could work in colon cancers with genetic mutation, study finds

April 25, 2011
A class of drugs that shows promise in breast and ovarian cancers with BRCA gene mutations could potentially benefit colorectal cancer patients with a different genetic mutation, a new study from the University of Michigan ...

Researchers discover genes involved in colorectal cancer

November 6, 2011
A jumping gene with the fairy tale name "Sleeping Beauty" has helped to unlock vital clues for researchers investigating the genetics of colorectal cancer.

Potential treatment target for KRAS-mutated colon cancer found

February 16, 2012
Researchers from the Massachusetts General Hospital (MGH) Cancer Center have identified a new potential strategy for treating colon tumors driven by mutations in the KRAS gene, which usually resist both conventional and targeted ...

Possible link between bacterium, colon cancer found

October 17, 2011
For the first time, a specific microorganism has been found to be associated with human colorectal cancer. In two studies published online today in Genome Research, independent research teams have identified Fusobacterium ...

Combination therapies for drug-resistant cancers

October 10, 2011
Some cancers can be effectively treated with drugs inhibiting proteins known as receptor tyrosine kinases, but not those cancers caused by mutations in the KRAS gene. A team of researchers led by Jeffrey Engelman, at Massachusetts ...

Recommended for you

Outdoor light at night linked with increased breast cancer risk in women

August 17, 2017
Women who live in areas with higher levels of outdoor light at night may be at higher risk for breast cancer than those living in areas with lower levels, according to a large long-term study from Harvard T.H. Chan School ...

Scientists develop novel immunotherapy technology for prostate cancer

August 17, 2017
A study led by scientists at The Wistar Institute describes a novel immunotherapeutic strategy for the treatment of cancer based on the use of synthetic DNA to directly encode protective antibodies against a cancer specific ...

Scientists develop blood test that spots tumor-derived DNA in people with early-stage cancers

August 16, 2017
In a bid to detect cancers early and in a noninvasive way, scientists at the Johns Hopkins Kimmel Cancer Center report they have developed a test that spots tiny amounts of cancer-specific DNA in blood and have used it to ...

Toxic formaldehyde is produced inside our own cells, scientists discover

August 16, 2017
New research has revealed that some of the toxin formaldehyde in our bodies does not come from our environment - it is a by-product of an essential reaction inside our own cells. This could provide new targets for developing ...

Cell cycle-blocking drugs can shrink tumors by enlisting immune system in attack on cancer

August 16, 2017
In the brief time that drugs known as CDK4/6 inhibitors have been approved for the treatment of metastatic breast cancer, doctors have made a startling observation: in certain patients, the drugs—designed to halt cancer ...

Researchers find 'switch' that turns on immune cells' tumor-killing ability

August 16, 2017
Molecular biologists led by Leonid Pobezinsky and his wife and research collaborator Elena Pobezinskaya at the University of Massachusetts Amherst have published results that for the first time show how a microRNA molecule ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.