Genetic Drivers of Aggressive Prostate Cancer, Study Reveals
Scientists from UCLA, the University of Toronto and the University of Melbourne have uncovered new genetic clues that explain why some prostate cancer remain slow-growing while others become life-threatening.
The findings, published in Cancer Discovery, evaluated the roles of inherited genetic factors passed down from our parents and somatic mutations acquired during tumor formation. The research shows that germline and somatic variability work together to initiate and drive progression of prostate cancer. This discovery could one day help improve how doctors predict and treat aggressive cancers.
The interaction between inherited genetic factors and the timing of mutations in the tumor’s DNA is central to understanding how prostate cancer evolves,” said Dr. Paul Boutros, professor of urology and human genetics at the David Geffen School of Medicine at UCLA, director of cancer data science at the UCLA Health Jonsson Comprehensive Cancer Center and co-senior author of the study. “We found that prostate cancer follows a common evolutionary path, with different tumors branching off depending on early genetic changes and an individual’s inherited genetic background. Some tumors may become aggressive because of specific mutations, while others remain indolent. Both genetic randomness and inherited traits play a role in determining these outcomes.
Researchers used whole-genome sequencing to analyze the complete genomes of 666 localized prostate tumors — the largest whole-genome dataset of its kind — covering the full range from mild to aggressive cases. The researchers identified 223 regions of the genome frequently mutated in prostate tumors that help cancer grow and spread. Most of these were undetectable using traditional targeted sequencing methods deployed in clinical assays.
“This study offers a new way of thinking about prostate cancer risk assessment,” said Boutros, who also serves as the interim vice dean for research at the David Geffen School of Medicine at UCLA, and is the associate director of cancer informatics at the UCLA Institute for Precision Health. “By combining inherited genetic markers with tumor sequencing, we could one day more accurately predict which cancers are likely to become aggressive and uncover new ways to prevent aggressive prostate cancer before it develops.”
Ref: Takafumi N. Yamaguchi, Kathleen E. Houlahan et al. The Germline and Somatic Origins of Prostate Cancer Heterogeneity: Cancer Discov (2025). https://doi.org/10.1158/2159-8290.CD-23-0882
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