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Prostate Cancer Cases in China Show Recurrent Alterations Distinct From Western Cohorts

NEW YORK – A team from China and the US has shared findings from a genomic, transcriptomic, and epigenomic analysis of hundreds of prostate cancer cases in China and found that they harbor recurrent mutations that differ from those seen in patients from Western countries.

"Alterations of the genome and epigenome were correlated and were predictive of disease phenotype and progression," the researchers reported, noting that the broader mutations and epigenetic changes identified in the cases "converged on pathways that are important for prostate cancer, providing insights into this devastating disease." The work was led by co-senior authors Yinghao Sun and Xu Gao, urology researchers at the Second Medical University in Shanghai, and co-senior author Ting Wang at Washington University.

As they reported in Nature on Wednesday, the researchers used whole-genome sequencing, RNA sequencing, microRNA sequencing, and whole-genome bisulfite sequencing to search for somatic mutations, expression shifts, and methylation changes in tumor samples from more than 200 Chinese men with localized prostate cancer.

The resulting data set — which the team dubbed the "Chinese Prostate Cancer Genome and Epigenome Atlas" (CPGEA) — pointed to FOXA1 mutations and other alterations that appeared to be overrepresented in the prostate cancer cases. Those somatic alterations turned up far less frequently in thousands of tumor samples from prostate cancer patients in Western countries, which have previously been found to have frequent ETS fusions between TMPRSS2 and ETS transcription factor genes.

"Comparative analysis of samples from CPGEA and Western cohorts revealed marked disparities in the mutational landscape of the same disease," the authors reported. "Although ETS fusions have long been regarded as the flagship mutation for prostate cancer, our study indisputably positions FOXA1 mutations as the most prominent signature in Chinese populations."

For their study, the researchers focused on tumor and matched normal tissue from 208 men from China who were treated for primary prostate cancer with radical prostatectomy surgery. They noted that their comparative genomic, transcriptomic, and epigenomic analyses centered on 177 of those tumors, which had not been subjected to prior treatment.

Among other alterations in the tumors — including genomic and epigenomic features that coincided with specific prostate cancer features or progression — the team saw FOXA1 gene mutations in 41 percent of the tumors, as well as recurrent ZNF292 and CHD1 gene deletions in around 18 percent of tumors.

Those genetic changes and other 'omic profiles in the newly-sequenced prostate tumors differed from those present in already available data for 2,554 prostate cancer patients from other parts of the world, including more than a dozen Western cohorts. Prior studies have shown that more than half of prostate cancers in the West are marked by ETS fusions, they noted.

"The frequency and unique pattern of FOXA1 mutations in Chinese prostate cancer underscores the need to investigate the oncogenic mechanism of individual mutations, as well as factors that predispose Chinese individuals to them," the authors wrote.