• DOI:10.1038/s42003-020-01175-x
• Corpus ID: 221118233

Genetic alterations in the 3q26.31-32 locus confer an aggressive prostate cancer phenotype

@article{Simpson2020GeneticAI,
  title={Genetic alterations in the 3q26.31-32 locus confer an aggressive prostate cancer phenotype},
  author={Benjamin S. Simpson and Niedzica Camacho and Hayley J. Luxton and Hayley Pye and Ron Finn and Susan Heavey and Jason J. Pitt and Caroline M. Moore and Hayley C. Whitaker},
  journal={Communications Biology},
  year={2020},
  volume={3}
}

• B. Simpson, N. Camacho, +6 authors H. Whitaker
• Published 14 August 2020
• Biology
• Communications Biology

Large-scale genetic aberrations that underpin prostate cancer development and progression, such as copy-number alterations (CNAs), have been described but the consequences of specific changes in many identified loci is limited. Germline SNPs in the 3q26.31 locus are associated with aggressive prostate cancer, and is the location of NAALADL2 , a gene overexpressed in aggressive disease. The closest gene to NAALADL2 is TBL1XR1 , which is implicated in tumour development and progression. Using publicly-available cancer genomic data we report that NAALADL2 and TBL1XR1 gains/amplifications are more prevalent in aggressive sub-types of prostate cancer when compared to primary cohorts. In primary disease, gains/amplifications occurred in 15.99% (95% CI: 13.02–18.95) and 14.96% (95% CI: 12.08–17.84%) for NAALADL2 and TBL1XR1 respectively, increasing in frequency in higher Gleason grade and stage tumours. Gains/amplifications result in transcriptional changes and the development of a pro-proliferative and aggressive phenotype. These results support a pivotal role for copy-number gains in this genetic region. Benjamin Simpson et al. use publicly available cancer genomic data to investigate copy number changes at the 3q26.31–32 locus, which has been associated with aggressive prostate cancer based on single-nucleotide polymorphisms. They find that gains of NAALADL2 and TBL1XR1 in this locus are associated with more aggressive subtypes of prostate cancer and the transcription of pro-proliferative signalling processes.