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.

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.