Replication-incompetent gammaretroviral and lentiviral vector-based insertional mutagenesis screens identify prostate

Victor M Bii1, Casey P Collins1, Jonah D Hocum1

  • 1College of Pharmacy, Washington State University, Spokane 99210, WA, USA.

Oncotarget
|April 13, 2018
PubMed

Insights

This study used gammaretroviral (γRV) and lentiviral (LV) vectors to identify genes driving prostate cancer progression. Complementary vector approaches revealed new candidate genes and potential biomarkers for predicting recurrence risk in patients.

Area of Science:

  • Oncology
  • Genetics
  • Molecular Biology

Background:

  • Insertional mutagenesis screens using replication-incompetent gammaretroviral (γRV) and lentiviral (LV) vectors are established methods for identifying cancer driver genes.
  • These vectors integrate into the host genome, potentially dysregulating nearby genes and leading to cancer development.
  • γRV and LV vectors possess distinct integration profiles and genotoxic potentials, suggesting they can serve as complementary tools for mutagenesis screens.

Purpose of the Study:

  • To identify driver genes involved in the progression of androgen-independent prostate cancer (AIPC).
  • To leverage the complementary strengths of both γRV and LV vectors in insertional mutagenesis screens.
  • To discover potential biomarkers and therapeutic targets for prostate cancer.

Main Methods:

  • Utilized a xenotransplant mouse model with orthotopically injected, vector-transduced LNCaP cells.
  • Induced an androgen-deficient environment through castration to promote metastatic tumor development.
  • Employed a high-throughput modified genomic sequencing PCR (MGS-PCR) to identify vector integration sites in metastatic tumors.

Main Results:

  • Identified thirteen candidate prostate cancer progression genes: OR2A14, FER1L6, TAOK3, MAN1A2, MBNL2, SERBP1, PLEKHA2, SPTAN1, ADAMTS1, SLC30A5, ABCC1, SLC7A1, and SLC25A24.
  • Found that the expression of TAOK3 and ABCC1 in prostate cancer patients predicted the risk of recurrence following androgen deprivation therapy.
  • Demonstrated the complementary utility of γRV and LV vectors in uncovering cancer driver genes.

Conclusions:

  • Gammaretroviral (γRV) and lentiviral (LV) vectors are complementary tools for identifying cancer driver genes.
  • The identified candidate genes, particularly TAOK3 and ABCC1, show promise as potential biomarkers for prostate cancer recurrence.
  • These findings highlight novel therapeutic targets for prostate cancer progression.

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