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miRNA Expression Analyses in Prostate Cancer Clinical Tissues
Published on: September 8, 2015
High frequency of the SDK1:AMACR fusion transcript in Chinese prostate cancer
Yanling Zhang1, Xue-Ying Mao2, Xiaoyan Liu3
1Department of Pathology, The First Affiliated Hospital, Zhejiang University Medical College Hangzhou, China ; Department of Gynecology and Obstetrics, Sir Run Run Shaw Hospital, Zhejiang University Medical College Hangzhou, China.
Abstract:
Chromosomal rearrangements and fusion genes play important roles in tumor development and progression. Four high-frequency prostate cancer (CaP) specific fusion genes, SDK1:AMACR, RAD50:PDLIM4, CTAGE5:KHDRBS3 and USP9Y:TTTY15 have been reported in Chinese CaP samples through a transcriptome sequencing study. We previously reported that USP9Y:TTTY15 is a transcription-mediated chimeric RNA, which is expressed in both tumor and non-malignant samples, and here we attempted to confirm the existence of the other three fusion genes SDK1:AMACR, RAD50:PDLIM and CTAGE5:KHDRBS3. We detected SDK1:AMACR fusion transcript in 23 of 100 Chinese CaP samples, but did not detect RAD50:PDLIM4 and CTAGE5:KHDRBS3 transcripts in any of those samples. SDK1:AMACR fusion transcript is Chinese CaP specific, which was neither detected in non-malignant prostate tissues adjacent to cancer from Chinese patient nor in CaP samples from UK patients. However, we did not detect genomic rearrangement of SDK1 gene by fluorescence in situ hybridization analysis, indicating that SDK1:AMACR is also a transcription-mediated chimeric RNA. Quantitative analysis demonstrated that high level AMACR expression was associated with SDK1:AMACR fusion status (P=0.004), suggesting that SDK1:AMACR fusion transcript may promote prostate carcinogenesis through increasing AMACR expression. However, the fusion status was not significantly correlated with any poor disease progression clinical features. The identification of the SDK1:AMACR fusion transcript in CaP cases from China but not from UK further supports our previous observation that different genetic alterations contribute to CaP in China and Western countries, although many genetic changes are also shared. Further studies are required to establish if CaPs with SDK1:AMACR represent a distinct subtype.
Insights
A novel prostate cancer (CaP) fusion gene, SDK1:AMACR, was identified in Chinese patients. This transcription-mediated chimeric RNA is linked to higher AMACR expression but not disease progression, suggesting a potential role in CaP development.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Chromosomal rearrangements and fusion genes are implicated in cancer development.
- Previous studies identified four high-frequency prostate cancer (CaP) specific fusion genes in Chinese CaP samples.
- USP9Y:TTTY15 was previously characterized as a transcription-mediated chimeric RNA.
Purpose of the Study:
- To confirm the existence of three other high-frequency CaP-specific fusion genes: SDK1:AMACR, RAD50:PDLIM4, and CTAGE5:KHDRBS3.
- To investigate the nature and potential role of the SDK1:AMACR fusion transcript in prostate cancer.
Main Methods:
- Transcriptome sequencing was used to identify fusion genes.
- RT-PCR was employed to detect fusion transcripts.
- Fluorescence in situ hybridization (FISH) was utilized to analyze genomic rearrangements.
- Quantitative analysis assessed the correlation between fusion status and gene expression/clinical features.
Main Results:
- The SDK1:AMACR fusion transcript was detected in 23% of Chinese CaP samples.
- RAD50:PDLIM4 and CTAGE5:KHDRBS3 fusion transcripts were not detected.
- FISH analysis indicated that SDK1:AMACR is a transcription-mediated chimeric RNA, not due to genomic rearrangement.
- High AMACR expression was significantly associated with the SDK1:AMACR fusion status (P=0.004).
- The fusion status did not correlate with poor disease progression.
- SDK1:AMACR was specific to Chinese CaP and not found in adjacent non-malignant tissues or UK CaP samples.
Conclusions:
- SDK1:AMACR is a transcription-mediated chimeric RNA specific to Chinese prostate cancer.
- This fusion may contribute to prostate carcinogenesis by increasing AMACR expression.
- The SDK1:AMACR fusion does not appear to be a marker for aggressive disease.
- Findings suggest potential ethnic-specific genetic alterations in prostate cancer, warranting further investigation into SDK1:AMACR as a distinct subtype marker.

