Cancer Research Uncovers New Clues to Biological Function

One of my favorite things about science is the surprise factor. The course of scientific progress is charted by a mix of plodding, incremental changes and completely unexpected new discoveries that change how we understand ourselves and the world around us.

Last week’s annual meeting of the American Association for Cancer Research was full of talks that fall into the category of “we thought biology worked a certain way, but when we took a closer look, we found all sorts of things we never expected.” As a reporter, that’s far and away the most fun category to work with.

Here’s a summary of two of those surprise discoveries from this year’s AACR meeting — all with significant potential to change how we treat or possibly even prevent cancer in the future. (Far, far in the future. It’s a research meeting, after all.) And don’t let the scientific jargon put you off. I’ll explain it as we go.

Extrachromosomal DNA

The DNA in our cells holds our genes, and they’re nicely packaged into chromosomes — think of them like long shoelaces that get wadded up to fit inside each cell. DNA sequencing works by straightening out those shoelaces and reading the biological building blocks one by one.

But Paul Mischel, a scientist at Stanford Medicine, and his team discovered that this tidy organizational system isn’t followed by all cells. In tumor cells, there’s something called extrachromosomal DNA — snippets of DNA that somehow detached from chromosomes and float around on their own. The discovery itself isn’t new, but the team’s recognition of its prevalence is. Conventional wisdom among scientists was that this phenomenon was incredibly rare, happening in just 1% or so of cancer cells. But Mischel’s team analyzed thousands of cancer samples and found that about 17% of tumors carried extrachromosomal DNA. “Things were not actually where we thought they were,” Mischel told AACR attendees.

So why does that matter? As it turns out, these free-floating DNA snippets don’t abide by the same rules as chromosomes when cells divide. Certain daughter cells of each tumor cell may contain a lot more of this type of DNA than they’re supposed to, and that can drive differences in tumor evolution more than scientists would expect based on normal cell division.

When cancer-causing genes are located on extrachromosomal DNA, the effect on tumor evolution can be linked to more advanced cancers, metastatic cancers, and cancers that are resistant to treatment. With this key knowledge, scientists may be able to use more advanced analysis technologies to figure out not just which genes are present in a tumor, but whether they’re located on or off chromosomes. One day, that could improve treatment selection for patients with cancer.

Microproteins

Another great example of a new discovery came from John Prensner at the University of Michigan, whose lab aims to shine a light on the “dark proteome.” (If the genome is all of your genes, the proteome is all of your proteins.) Just like dark matter in the universe, the dark proteome refers to all those proteins that must exist and be informing our biology, but haven’t been found yet.

Prensner’s team has yanked some elements out of that darkness and into the light. So-called microproteins represent a new frontier in cancer research, he said. These tiny proteins — so small that they’ve been missed because they don’t meet standard definitions for what a protein looks like — appear to interact with other proteins and have a noticeable biological impact.

According to Prensner, who began looking at microproteins in breast cancer samples and is now studying them in a type of brain cancer, dozens of these itty-bitty proteins have been identified so far. He believes there are thousands more waiting to be discovered — and that the constellation of microproteins found in cancer will be different from those found in healthy cells.

In the future, a search for these microproteins in cancer samples could give scientists and clinicians a better way to predict cancer progression or to match patients to the therapies that will be most effective for them.

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