Hallmark cancer gene regulates RNA ‘dark matter’: Novel findings are a promising step in the development of new tests for cancer early detection

A key genetic mutation that occurs early on in cancer alters RNA “dark matter” and causes the release of previously unknown RNA biomarkers for cancer early detection, a new study by UC Santa Cruz researchers published in the journal Cell Reports shows.

Researchers examined the effects of mutations in the KRAS gene, which is among the most frequently mutated genes across all cancers, including pancreatic, lung, and colorectal cancers. KRAS is thought to be an initial “driver” mutation that leads to cancer formation, making it essential for understanding and detecting cancer at its earliest stages.

In this study, Assistant Professor of Biomolecular Engineering Daniel Kim’s lab focused on KRAS mutations in lung cancer to determine their effects on RNA “dark matter,” which is generated from 75% of the 3 billion base pairs in the human genome, with the goal of discovering new RNA biomarkers for cancer early detection.

“The sooner you detect that someone has cancer, the more likely they will be to survive through treatment and surgery,” said Kim, who is affiliated with the UC Santa Cruz Genomics Institute, the Institute for the Biology of Stem Cells, the Center for Molecular Biology of RNA, and is an Associate Member of the Canary Center at Stanford for Cancer Early Detection. “Millions of people die from cancer every year around the world, and there is an urgent need to develop highly sensitive and specific diagnostic tests that enable cancer early detection, before it has spread to other parts of the body.”

Kim’s lab studies how the KRAS gene regulates the transcriptome, all of the RNA produced in a cell. RNA’s most commonly recognized function is as a “messenger” that takes the encoded genetic information in DNA and converts this into protein, but recent advances in genomics have revealed that the vast majority of RNA is noncoding and does not make protein. Kim’s lab focuses on researching this noncoding RNA, with the goal of using this information to better understand the formation of cancer and to identify new biomarkers for cancer early detection.

In this study, led by Kim lab Ph.D. candidate in biomolecular engineering and National Institutes of Health F99/K00 fellow Roman Reggiardo, researchers found that KRAS mutations in lung cancers also activate interferon-stimulated genes, something that is seen in many cancers but the cause of which has been unclear.

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