Transcription-Mediated Chimeric RNAs in Prostate Cancer: Time to Revisit Old Hypothesis?

Abstract

Chromosomal rearrangements and fusion genes play important roles in tumor development and progression. Four high-frequency prostate cancer-specific fusion genes were recently reported in Chinese cases. We attempted to confirm one of the fusion genes, USP9Y-TTTY15, by reverse transcription PCR, but detected the presence of the USP9Y-TTTY15 fusion transcript in cancer samples, nonmalignant prostate tissues, and normal tissues from other organs, demonstrating that it is a transcription-induced chimeric RNA, which is commonly produced in normal tissues. In 105 prostate cancer samples and case-matched adjacent nonmalignant tissues, we determined the expression level of USP9Y-TTTY15 and a previously reported transcription-induced chimeric RNA, SLC45A3-ELK4. The expression levels of both chimeric RNAs vary greatly in cancer and normal cells. USP9Y-TTTY15 expression is neither higher in cancer than adjacent normal tissues, nor correlated with features of advanced prostate cancer. Although the expression level of SLC45A3-ELK4 is higher in cancer than normal cells, and a dramatic increase in its expression from normal to cancer cells is correlated with advanced disease, its expression level in cancer samples alone is not correlated with any clinical parameters. These data show that both chimeric RNAs contribute less to prostate carcinogenesis than previously reported.

Clinical utility of a novel urine-based gene fusion TTTY15-USP9Y in predicting prostate biopsy outcome

“…Recently, an independent group confirmed existence of USP9Y-TTTY15 in prostate cancer tissues but did not find its relationship with prostate cancer progression, which warrant further functional and molecular studies [23]. Interestingly, we found that only Table 4 Univariable and multivariable logistic regression models in predicting any prostate cancer at prostate biopsy Variable TTTY15-USP9Y could be stably detected in the post-DRE urine samples and could further help to predict the prostate biopsy outcome.…”

RNA sequencing unravels the genetics of refractory/relapsed T-cell acute lymphoblastic leukemia. Prognostic and therapeutic implications

“…We identified 183 predicted fusion transcripts (median 6/sample; range, 0-36) (Online Supplementary Table S6A) predominantly involving genes localized next to each other on the same chromosome, and likely representing read-through of transcription. 15,20 For example, two fusion transcripts involving adjacent genes, namely SMG5-PAQR6 (n=2) and TTTY15-USP9Y (n=2), previously described in prostatic cancer [21][22][23] and also identified in two cases of our validation cohort, were detected in normal thymus cells from healthy donors.…”

Ampullary Cancers Harbor ELF3 Tumor Suppressor Gene Mutations and Exhibit Frequent WNT Dysregulation

“…Fusion analysis identified 2 noticeable non-recurrent fusions: SLC45A3-ELK4 used as a prognosis marker in prostate cancer where its expression is elevated (Kumar-Sinha et al, 2012; Ren et al, 2014); and a LINE- MET fusion in a patient without any KRAS or TP53 driving mutations and a high MET expression (Figure S4, Table S5). LINE element insertions are found in PDAC, colon, hepatocellular, oesophageal, and lung carcinoma (Paterson et al, 2015; Rodic et al, 2015).…”