Study provides new understanding of mitochondria genome with potential for new avenues of treatment for multiple cancers

HOUSTON ― A study led by The University of Texas MD Anderson Cancer Center furthered understanding about mitochondria, the cell components known as the “powerhouse of the cell.” Knowing more about the genome is crucial given that mitochondria play important roles in tumorigenesis.

Findings were published in the Feb. 5 online issue of Nature Genetics and resulted through collaboration with the International Cancer Genome Consortium—The Cancer Genome Atlas Pan—Cancer Analysis of Whole Genomes (PCAWG) project, an effort involving more than 1,300 scientists and clinicians from 37 countries. Since its inception, the PCAWG has analyzed more than 2,600 genomes across 38 tumor types.

“This study lays a foundation for translating mitochondrial biology into clinical applications,” said Han Liang, Ph.D., professor of Bioinformatics & Computational Biology. “Our analysis presents the most definitive mutational landscape of mitochondrial genomes and identifies several hyper-mutated cases. Such truncated mutations are remarkably enriched in kidney, colorectal and thyroid cancers, suggesting oncogenic impact with the activation of signaling pathways.”

Mitochondria are crucial cellular organelles, with a single human cell containing several hundred mitochondria. The cell components play essential roles in generating most of the cell’s energy through a process known as oxidative phosphorylation. The mitochondrial genome encodes 13 proteins that form respiratory chain complexes with other proteins.

“The involvement of mitochondria in carcinogenesis has long been suspected because altered energy metabolism is a common feature of cancer,” said Liang. “Furthermore, mitochondria play important roles in other tasks, such as biosynthesis, signaling, cellular differentiation, cell growth and death.”

The team found that the mitochondrial genome is an essential component in understanding the complex molecular patterns observed in cancer genomes and helping to pinpoint potential cancer driver events.

“Our results underscore the clinical importance of mitochondria. This study has untangled and characterized the full spectrum of molecular alterations of mitochondria in human cancers,” said Liang. “We have highlighted the function of mitochondrial genes in oxidative phosphorylation, DNA repair and cell cycle, showing their connections with clinically actionable genes.”

MD Anderson study team members included Yuan Yuan, Ph.D.; Jun Li, Ph.D.; and John Weinstein, M.D., Ph.D., all of the Department of Bioinformatics & Computational Biology.

The study was funded by the Lorraine Dell Program in Bioinformatics for Personalized Cancer Medicine; an MD Anderson Faculty Scholar Award; the Institute of Information & Communications Technology (B0101-15-0104); the Development of Supercomputing System for the Genome Analysis; the Korea Health Industry Development Institute (KHIDI); the Ministry of Health & Welfare, Republic of Korea (H114C0072 and H117C1836); and the Korean National Research Foundation (NRF-2016R1D1A1B03934001 and NRF-2017R1A2B2012796). Liang reported no disclosures.

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About MD Anderson The University of Texas MD Anderson Cancer Center in Houston ranks as one of the world’s most respected centers focused on cancer patient care, research, education and prevention. The institution’s sole mission is to end cancer for patients and their families around the world. MD Anderson is one of only 50 comprehensive cancer centers designated by the National Cancer Institute (NCI). MD Anderson is ranked No.1 for cancer care in U.S. News & World Report’s “Best Hospitals” survey. It has ranked as one of the nation’s top two hospitals for cancer care since the survey began in 1990, and has ranked first 15 times in the last 18 years. MD Anderson receives a cancer center support grant from the NCI of the National Institutes of Health (P30 CA016672).

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