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Colorectal Cancer Molecules and Genes Reveal Surprises

Genome sequencing lab — NIH

A Labor Day salute to the hard-working scientists—doctors, PhDs, lab techs, technology inventors—who have done some  heavy lifting to peer into the tiniest recesses of cells, genes, and molecules to unravel what makes colorectal cancer happen.

In the widest and deepest effort to date, the Cancer Genome Atlas Project has produced some surprises and key clues about colorectal cancer, published recently in the journal Nature.

It was almost “ industrial-strength genetics to try to unpick and take apart the genetic coding,” according to Dr. David Kerr, professor at the University of Oxford and Past President of the European Society for Medical Oncology. 

One of the surprises for colorectal cancer—the third cancer they’ve analyzed—is that “colon and rectal cancer are genetically virtually indistinguishable,” said Kerr. “This puts to rest a mythology …that rectal and colon cancers are somehow different beasts… There is no molecular basis for that whatsoever. They have put that mythology to bed.”

Industrial-strength effort

That kind of paradigm shift in understanding a cancer can only come from a huge joint effort of many scientists. The Cancer Genome Atlas Project, funded by the National Cancer Institute—is a collaboration of more than 150 researchers at dozens of institutions across the U.S. working to unravel the genetic events in 20 cancers. Colorectal cancer is the third cancer tackled by the project.

For the first time ever, the researchers completed a whole-genome analysis of about 250 different colorectal cancers. Rather than just looking for mutations (changes) in a few genes, the researchers methodically mapped each cancer cell’s whole genome–all of its DNA packaged in 3.5 billion pairs of the 4-letter genetic “alphabet.” By comparing 224 cancerous and normal cell pairs, they found and classified every mutation in every gene—whether it was a missing chunk of DNA, a switched letter order, a broken chain—that occurred in the cancer cells.  

When they compared all of the genetic changes in 276 different colorectal tumors, they could see patterns where the cancers shared certain gene mutations or cell proteins acting abnormally.

Surprise: colon and rectal cancer is the same  

The first and perhaps biggest surprise, as Dr. Kerr noted, was that colon and rectal cancers are exactly the same, at least on a cellular or molecular level. Although anatomical differences mean that surgery and radiation treatments will still differ, doctors now know that the cancers in either location can be exactly the same, perhaps responding to chemotherapy the same way.

“This finding of the true genetic nature of colon and rectal cancers is an important achievement…that [has] the potential to change the way we diagnose and treat certain cancers,” said Dr. Francis Collins, director of the National Institutes of Health.

 “Vanilla” colorectal cancer will become many flavors

The meticulous review also found new genetic mutations. The researchers found 24 genes that were mutated in a significant number of the cases—including three new genes. (One, the SOX9 gene, is involved with epithelial stem cells—another current line of CRC research.) They found two other genes that were “over-expressed”—too active in cell proliferation. They also identified changes in three different “signaling pathways” that turn genes on or off during cell growth)—most consistently in the WNT pathway. 

All of these discoveries will help scientists define different sub-types of colorectal cancer. This federally funded basic science research gives new targets for private companies to target new treatments, plus diagnostic tests. Clinical researchers will begin making connections between types of different genetic or cell changes seen under a microscope and how the tumors appear, grow, or recur in real people.

Eventually, doctors will have diagnostic tests to define different subtypes of colorectal cancer; they will know which treatment works best against that type of cancer cell; and how to best monitor that person for recurrent cancer. 

What this means for you

For those of you coping with the effects of CRC— either missing a loved one over this holiday weekend, or sitting alone in your room coping with unglamorous nausea, fatigue, diarrhea—know that there’s a huge team of scientists behind you, laboring in their government-funded or private company labs to understand and fight this disease.

You have a powerful, dedicated team working hard for you this Labor Day.

For some light weekend reading, here is a primer on genomes, mutations, and cancer. 

Sources: Original article at Nature, Vol. 487, 19 July 2012, p. 330-335; news release, National Human Genome Research Institute; Medscape video/transcript, 8/6/2012.

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One Comment;

  1. debbie said:

    I am going on my 5th. Yr. Of metz.colon cancer, they day thats the limit, I get to live for 5 years with this disease. Its almost time up for me, I am 56 yrs. Old I have 6 children and 8 grandchildren, I dont want to die! But if your research can help other people down the Road, Then God Bless Your whole team. Thankyou so very much, for caring for People like me. Truly Deb Mitchell

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