Analysis of Unexplored Part of Human Genome May Lead to Cancer Biomarker Development
A new analysis opens the door to the discovery of thousands of potential new cancer biomarkers, according to a recent study by Iyer et al published in Nature Genetics.
Long Noncoding RNA
Researchers at the University of Michigan Comprehensive Cancer Center analyzed the global landscape of long noncoding RNAs (lncRNAs), a portion of the genome that has not been previously well explored. This vast portion of the human genome has been considered “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 cancer diagnosis, prognosis, and treatment.
“We know about protein-coding genes, but that represents only 1% to 2% of the genome. Much less is known about the biology of the noncoding genome in terms of how it might function in a human disease like cancer,” said senior study author Arul M. Chinnaiyan, MD, PhD, Director of the Michigan Center for Translational Pathology and S.P. Hicks Professor of Pathology at the University of Michigan Medical School.
Study Details
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.
“We used all of this data to decipher what the genomic landscape looks like in different tissues as well as in cancer,” Dr. Chinnaiyan said. “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, 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 metastatic prostate cancer than in early-stage disease. SChLAP1 was found primarily in prostate cancer cells, not in other cancers or normal cells, which gives researchers hope that a noninvasive 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 prostate cancer.
“Some long noncoding RNAs tend to be exquisitely specific for cancer, while protein-coding genes are often not. That’s what makes lncRNAs a very promising target for developing biomarkers,” Dr. Chinnaiyan said. “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.”
Dr. Chinnaiyan is the corresponding author for the Nature Genetics article.
Oncomine is supported by ThermoFisher, Inc (previously Life Technologies and Compendia Biosciences). Dr. Chinnaiyan was a cofounder of Compendia Biosciences and served on the scientific advisory board of Life Technologies before it was acquired. The University of Michigan has filed a patent application for the use of a subset of the lcRNAs described in this study as biomarkers of cancer.
The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.
