Researchers open 'Pandora's box' of potential cancer biomarkers

January 20, 2015 by Nicole Fawcett, University of Michigan Health System
Arul Chinnaiyan, M.D., Ph.D. Credit: University of Michigan Health System

A new analysis opens the door to discovery of thousands of potential new cancer biomarkers.

Researchers at the University of Michigan Comprehensive Cancer Center analyzed the global landscape of a portion of the genome that has not been previously well-explored - long non-coding RNAs. This vast portion of the human genome has been considered the dark matter because so little is known about it. Emerging new evidence suggests that lncRNAs may play a role in cancer and that understanding them better could lead to new potential targets for improving , prognosis or treatment.

"We know about protein-coding genes, but that represents only 1-2 percent of the genome. Much less is known about the biology of the non-coding in terms of how it might function in a human disease like cancer," says senior study author Arul M. Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology and S.P. Hicks Professor of Pathology at the University of Michigan Medical School.

The researchers pulled together 25 independent datasets totaling 7,256 RNA sequencing samples. The data was from public sources such as The Cancer Genome Atlas project, as well as from the Michigan Center for Translational Pathology's archives. They applied high-throughput RNA sequencing technology to identify more than 58,000 lncRNA genes across normal tissue and a range of common cancer types.

Results of the study appear online in Nature Genetics.

"We used all of this data to decipher what the genomic landscape looks like in different tissues as well as in cancer," Chinnaiyan says. "This opens up a Pandora's box of all kinds of lncRNAs to investigate for biomarker potential."

The complete dataset, named the MiTranscriptome compendium, has been made available on a public website, http://www.mitranscriptome.org, for the scientific community to explore.

The researchers also identified one lncRNA, SChLAP1, as a potential biomarker for aggressive prostate cancer. SChLAP1 was more highly expressed in than in early stage disease. SChLAP1 was found primarily in , not in other cancers or normal cells, which gives researchers hope that a non-invasive test could be developed to detect SChLAP1. Such a test could be used to help patients and their doctors make treatment decisions for early stage .

"Some long non-coding RNAs tend to be exquisitely specific for , while protein-coding genes are often not. That's what makes lncRNAs a very promising target for developing biomarkers," Chinnaiyan says. "We hope that researchers will investigate the MiTransciptome compendium and begin to nominate lncRNAs for further study and development. It's likely that only a subset of these have true function but as a previously untapped area, it holds great promise."

Explore further: Team finds new genetic anomalies in lung cancer

More information: Nature Genetics, DOI: 10.1038/ng.3192 published online Jan. 19, 2015

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2 comments

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antialias_physorg
5 / 5 (4) Jan 20, 2015
"This opens up a Pandora's box of all kinds of lncRNAs to investigate for biomarker potential."

I don't think "Pandora's box" means what he thinks it means (he might heave been looking for the word 'cornucopia')
JVK
1 / 5 (2) Jan 20, 2015
See also: http://genomebiol...5/12/537

"A considerable proportion of TEs in the exonic transcriptome lies in lncRNAs [24],[25]. The myriad lncRNAs implicated for critical roles in development [54]-[56] and disease [57],[58] emphasize the need for improved understanding of lncRNA function. A modular domain structure for lncRNAs has been hypothesized [59] but has, thus far, eluded a thorough characterization. Our observation that TE sequences contain functional RBP binding sites represents an important step towards characterizing TEs as one type of modular domain in lncRNAs where RBP-TE interactions may function."

This indicates others are beginning to understand the complexities of cell type differentiation. We will soon be rid of those who think in terms of mutations and evolution.

Excerpt 2) Through a variety of mechanisms acting on RNA, such as splicing, localization, and degradation, post-transcriptional regulation by RBPs also modulates protein abundance.

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