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Updated: Feb 8, 2026

Isolation of Cancer Stem Cells From Human Prostate Cancer Samples
07:16

Isolation of Cancer Stem Cells From Human Prostate Cancer Samples

Published on: March 14, 2014

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Inactivation of CDK12 Delineates a Distinct Immunogenic Class of Advanced Prostate Cancer

Yi-Mi Wu1, Marcin Cieślik1, Robert J Lonigro2

  • 1Michigan Center for Translational Pathology, University of Michigan, Ann Arbor, MI 48109, USA; Department of Pathology, University of Michigan, Ann Arbor, MI 48109, USA.

Cell
|June 16, 2018
PubMed

Insights

A new prostate cancer subtype with CDK12 loss was discovered in metastatic castration-resistant prostate cancer (mCRPC). This subtype, characterized by gene fusions and elevated neoantigens, may respond to immune checkpoint immunotherapy.

Area of Science:

  • Oncology
  • Genomics
  • Cancer Biology

Background:

  • Metastatic castration-resistant prostate cancer (mCRPC) is a heterogeneous disease.
  • Understanding molecular subtypes is crucial for targeted therapies.

Purpose of the Study:

  • To identify novel molecular subtypes within mCRPC.
  • To characterize the genomic and clinical features of these subtypes.

Main Methods:

  • Integrative genomic analysis of 360 mCRPC samples.
  • Identification of genetic alterations, including biallelic CDK12 loss and focal tandem duplications (FTDs).
  • Analysis of gene expression, neoantigen burden, and tumor T cell infiltration.

Main Results:

  • A novel mCRPC subtype with biallelic CDK12 loss was identified, mutually exclusive with other known drivers.
  • CDK12 loss is associated with FTDs, increased gene fusions, and altered gene expression.
  • CDK12-mutant tumors exhibit elevated neoantigen burden and increased T cell infiltration, without homologous recombination deficiency signatures.

Conclusions:

  • CDK12 inactivation defines a distinct mCRPC subtype.
  • This subtype is characterized by unique genomic alterations and an inflamed tumor microenvironment.
  • CDK12-mutant mCRPC may represent a promising population for immune checkpoint immunotherapy.
Keywords:
CDK12focal tandem duplicationsgene fusionsimmunotherapymetastatic castration-resistant prostate cancerneoantigens

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