Oncogenic mechanisms of HOXB13 missense mutations in prostate carcinogenesis

Marta Cardoso1, Sofia Maia1, Paula Paulo1, Manuel R. Teixeira1,2,3

1 Cancer Genetics Group, IPO Porto Reseawrch Center (CI-IPOP), Portugese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal

2 Department of Genetics, Portugese Oncology Institute of Porto (IPO Porto), 4200-072 Porto, Portugal

3 Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto, 4050-313 Porto, Portugal

Correspondence to: Manuel R. Teixeira, email:

Keywords: HOXB13, germline mutations, prostate cancer, in vitro assays

Received: August 29, 2016 Accepted: September 23, 2016 Published: October 31, 2016


The recurrent germline mutation HOXB13 p.(Gly84Glu) (G84E) has recently been identified as a risk factor for prostate cancer. In a recent study, we have performed full sequencing of the HOXB13 gene in 462 Portuguese prostate cancer patients with early-onset and/or familial/hereditary disease, and identified two novel missense mutations, p.(Ala128Asp) (A128D) and p.(Phe240Leu) (F240L), that were predicted to be damaging to protein function. In the present work we aimed to investigate the potential oncogenic role of these mutations, comparing to that of the recurrent G84E mutation and wild-type HOXB13. We induced site-directed mutagenesis in a HOXB13 expression vector and established in vitro cell models of prostate carcinogenesis with stable overexpression of either the wild-type or the mutated HOXB13 variants. By performing in vitro assays we observed that, while the wild-type promotes proliferation, also observed with the F240L variant along with a decrease in apoptosis, the A128D mutation decreases apoptosis and promotes anchorage independent growth. No phenotypic impact was observed for the G84E mutation in the cell line model used. Our data show that specific HOXB13 mutations are involved in the acquisition of different cancer-associated capabilities and further support an oncogenic role for HOXB13 in prostate carcinogenesis.

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