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2020 Tad Smith & Caroline Fitzgibbons-PCF Young Investigator Award

Investigating the Pathological Role of AZI1 RNA in TMPRSS2-ERG Gene Fusion Formation

Sachin Kumar Gupta, PhD

Baylor College of Medicine

Mentors: Laising Yen, PhD

Description:

  • Certain genomic alterations are known to initiate the development of prostate cancer. One of the most frequent is gene fusion of the TMPRSS2 and ERG genes, which occurs in ~50% of cases. This alteration leads to overexpression of the ERG oncogene, which increases cell invasion and proliferation.
  • Prior studies have suggested that genomic rearrangements could be driven by RNA molecules that bind to regions of both chromosomes due to sequence homology.
  • Dr. Sachin Kumar Gupta is investigating whether RNAs may be responsible for directing the TMPRSS2-ERG gene fusion event that causes prostate cancer.
  • Dr. Gupta has identified a cellular RNA (“AZI1”) with a sequence partially resembling that of the TMPRSS2-ERG fusion RNA found in prostate cancer. Overexpression of this RNA could induces gene fusion between the TMPRSS2 and ERG genes in prostate cancer cells that did not previously have theTMPRSS2-ERG fusion.
  • In this project, Dr. Gupta will investigate the link between AZI1 RNA expression and TMPRSS2-ERG fusion formation. Whether AZI1 RNA expression correlates with TMPRSS2-ERG genomic fusions in prostate cancer clinical samples, and whether this relationship differs across racial/ethnic minority subpopulations, will be determined.
  • The molecular mechanisms by which AZI1 RNA drives formation of theTMPRSS2-ERG fusion will be determined.
  • If successful, this project will identify new mechanisms that drive prostate cancer-initiating genomic alterations, and potentially guide strategies to inhibit the development of future tumors.

What this means to patients: Dr. Gupta has discovered an RNA that may induce the gene fusions that drive the development of 50% of prostate cancer cases. This project will validate this phenomenon and describe its mechanisms, which may lead to new strategies to prevent the initiation of prostate cancer.