J Cancer 2021; 12(2):438-450. doi:10.7150/jca.48433

Research Paper

Whole-exome Sequencing of Prostate Cancer in Sardinian Identify Recurrent UDP-glucuronosyltransferase Amplifications

Tiansheng Zeng1,2, Maria Antonietta Fedeli3, Francesco Tanda3, Yuyong Wang4, Dongsheng Yang1, Bei Xue1, Lisha Jia1, Giuseppe Palmieri5, Leonardo A Sechi2✉, David J. Kelvin1,3,6,7✉

1. Division of Immunology, International Institute of Infection and Immunity, Shantou University Medical College, Shantou Guangdong, China.
2. Department of Biomedical Sciences, University of Sassari, Sassari, Italy.
3. Department of Scienze Mediche Chirurgiche e Sperimentali, first affiliated Hospital of 33445Sassari University.
4. Department of Urology, affiliated Hangzhou First People's Hospital, Zhejiang University School of Medicine, China.
5. Institute of Genetic and Biomedical Research (IRGB), Head, National Research Council (CNR), 07100 Sassari, Italy.
6. Department of Microbiology and Immunology, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4R2.
7. Canadian Center for Vaccinology, IWK, Halifax, Nova Scotia, Canada.

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Citation:
Zeng T, Fedeli MA, Tanda F, Wang Y, Yang D, Xue B, Jia L, Palmieri G, Sechi LA, Kelvin DJ. Whole-exome Sequencing of Prostate Cancer in Sardinian Identify Recurrent UDP-glucuronosyltransferase Amplifications. J Cancer 2021; 12(2):438-450. doi:10.7150/jca.48433. Available from https://www.jcancer.org/v12p0438.htm

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Abstract

Globally, prostate cancer is the third most common cancer in the world, and the second most common cancer in men. However, rates for incidence and mortality vary considerably with race, ethnicity, and geography. Over 97 significantly mutated genes that have been identified in prostate cancer; however, a lack of genomic prostate cancer studies focusing on different racial and ethnic groups and racial mixing pose a serious challenge to universalize these findings. The Sardinian population is an isolated Mediterranean population that has a high frequency of centenarians and a much lower incidence of prostate cancer than found in males in mainland Europe. Here, we conducted a genomic prostate cancer study on a Sardinian cohort diagnosed with local prostate cancer. Our data reveals a low rate of ERG fusion in Sardinian prostate cancer. Interestingly, we identified a novel BTBD7-SLC2A5 fusion that occurred in 13% of the patients. We also found that the UGT2B4 on 4q13.2 was amplified in 20% of the Sardinian patients but rarely amplified in patients of other population. These observations underscore the importance of the inter-population molecular heterogeneity of prostate cancer. In addition, we examined the expression of UGT2B4 in 497 prostate cancer patients derived from The Cancer Genome Atlas database. We found that high expression of UGT2B4 was associated with low-grade prostate cancer and upregulation of UGT2B4 in tumors was associated with upregulation of metabolism pathways such as 'de novo' IMP biosynthetic process, glutamine and monocarboxylic acid metabolism. These data provide insight into clinical relevance and functional mechanism of UGT2B4. Further understanding functional mechanism of UGT2B4 amplification and BTBD7-SLC2A5 fusion will aid in developing drugs to benefit the prostate cancer patients.

Keywords: UDP glucuronosyltransferase, BTBD7-SLC2A5 fusion, prostate cancer, Sardinian, whole exome sequencing