Exome sequencing identified six copy number variations as a prediction model for recurrence of primary prostate cancers with distinctive prognosis

Background: Prostate cancer (PCa) is a common type of malignancy, which represents one of the leading causes of death among men worldwide. Copy number variations (CNVs) and gene fusions play important roles in PCa and may serve as markers for the prognosis of this condition. Methods: We have presently conducted an analysis of CNVs and gene fusions in PCa, using whole exome sequencing (WES) data of primary tumors. For this, a cohort of 74 PCa patients, including 30 recurrent and 44 non-recurrent cases, were assessed during 5 years of follow-up. Results: We have identified 66 CNVs that were specific to the primary tumor tissues from the recurrent PCa group. Most of duplicated genomic regions were located in 8q2, suggesting that this chromosomal region could be important for the prognosis of PCa. Meanwhile, we have developed a random forest model, using six selected CNVs, with an accuracy near 90% for predicting PCa recurrence according to a 10-fold cross validation. In addition, we have detected 16 recurrent oncogenic gene fusions in PCa. Among these, ALK (ALK receptor tyrosine kinase)-involved fusions were the most common type of gene fusion (n=7). Four of these fusions (i.e., EML4-ALK, STRN-/ILI CLTC-ALK, ETV6-ALK) were previously identified in other cancer types, while the remaining three gene fusions (FRYL-ALK, ABLI-ALK, and BCR-ALK) were here identified. Conclusions: Our findings expand the current understanding in regard to prostate carcinogenesis. Current data might be further used for assay development as well as to predict PCa recurrence, using primary tissues.