162MO - Genomic characterization revealed from prospective clinical sequencing of 1016 Chinese prostate cancer patients

Background

Although disparities in prostate cancer (PCa) incidence and mortality among races have been well recognized, few biological factors driving disparities were identified, due to the lack of genomic data from minorities, including the Asian population.

Methods

A total of 1016 Chinese PCa patients, including 315 locoregional PCa, 313 metastatic castration-sensitive PCa (mCSPC) and 388 metastatic castration-resistant PCa (mCRPC), were prospectively enrolled and underwent targeted sequencing. Genomic data retrieved from the TCGA, MSKCC, and SU2C cohort was used as a comparator representing the White men. The genomic mutations were analyzed using an integrated bioinformatics strategy. The relationships between race and genomic mutations were evaluated using Fisher's exact test and multivariable logistic regression.

Results

Comparative analysis across disease stages revealed mutations in TP53, AR, FOXA1, and cell cycle pathway were enriched in mCRPC. Patients with visceral metastasis harbored more APC mutations compared with patients with bone metastasis. Genomic differences between races were mainly observed in castration-sensitive PCa, with tumors from Chinese men having more FOXA1 but less TP53 mutations in locoregional PCa and harboring fewer TP53, PTEN and APC mutations in mCSPC stage than those from White men. Unlike FOXA1 class-1 enriched in tumors from East Asian, FOXA1 class-2 was less common in East Asian patients and showed no enrichment in metastasis compared with primary cancer in East Asian cohort, in contrast to the findings in Western cohort.

Conclusions

The magnitude of difference in mutation prevalence between PCa from Chinese and White men varied across disease stages and was strongest in castration-sensitive disease. The lower frequency of FOXA1 class-2 mutations in Chinese PCa underscored the mechanistic difference in driving cancer progression between races. We call for more genomic data from minorities with rich clinical information to reduce widening racial disparity and accelerate our understanding of the interplay between germline and somatic mutations on PCa tumorigenesis and development.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Yao Zhu and Dingwei Ye.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.