Novel Mutated Genes, Pathways in Prostate Cancer Identified

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Researchers identified nearly 80 significantly mutated genes in prostate cancer, including many novel genes and pathways.
Researchers identified nearly 80 significantly mutated genes in prostate cancer, including many novel genes and pathways.

ORLANDO, FL Researchers identified nearly 80 significantly mutated genes in prostate cancer, including many novel genes and pathways not previously associated with the disease, according to a presentation at the 2017 Genitourinary Cancers Symposium.1

Joshua Armenia, PhD, a researcher in bioinformatics and genomics at Memorial Sloan Kettering Cancer Center in New York, New York, and colleagues conducted an aggregate, uniform analysis of 918 tumor and matched germline primary and metastatic prostate cancer whole exomes. There were 583 and 335 whole exomes from primary and metastatic tumors, respectively.

"We identified a total of 78 significantly mutated genes, including 37 not previously as significantly mutated genes in prostate cancer and 23 not previously identified as recurrently altered in cancer," said Dr Armenia.

The novel prostate cancer genes implicated in other tumor types include: SPEN, SETD2, ARID1A, CUL3, ARID2, SMARCAD1, and U2AF1. In addition, 14% of tumors harbored alterations in members of the ubiquitin pathway, where novel mutations in CUL3 were mutually exclusive with SPOP mutations.

"SPEN is a novel prostate cancer gene that was found in 10% of the 918 total tumors," noted Dr Armenia.

Investigators also identified a subclass of epigenetically mutated prostate cancer, representing 21% of all tumors evaluated, that are significantly enriched in prostate cancers lacking an ETS gene fusion.

In a comparison of primary and metastatic samples, Dr Armenia explained that TP53, AR, RB1, APC, and BRCA2 alterations and alterations in epigenetic regulators KMT2C and KMT2D were enriched in metastatic samples, while SPOP mutations and FOLP1/RYBP deletions were enriched in primary tumors.

RELATED: Immunotherapy and the Future of Prostate Cancer Treatment

These findings, which refined the map of somatic mutations in prostate cancer, may inform patient stratification and translational research.

Reference

  1. Armenia J, Mullane SA, Gao J, et al. The long tail of significantly mutated genes in prostate cancer. Paper presented at: 2017 Genitourinary Cancers Symposium; February 16-18, 2017; Orlando, FL.
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