Evidence map›Paper›PMID 37806842›Full record

ArticleEuropean urology oncology2024

Clinical and Functional Analyses of an African-ancestry Gain-of-function HOXB13 Variant Implicated in Aggressive Prostate Cancer.

Mayuko Kanayama, Yidong Chen, Daniel Rabizadeh, Lauren Vera, Changxue Lu, Sarah M Nielsen, Emily M Russell, Edward D Esplin, Hao Wang, William B Isaacs and 2 more

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in European urology oncology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.

0numbers the graph read from it
0cells of the map it votes in
10citing papers in PubMed
2.6field-weighted citation impact, top 9% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

10 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Article
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 1 country.

Mayuko KanayamaDepartment of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Yidong ChenGreehey Children's Cancer Research Institute, San Antonio, TX, USA; Department of Population Health Sciences, the University of Texas Health San Antonio, San Antonio, TX, USA.
Daniel RabizadehDepartment of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Lauren VeraDepartment of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Changxue LuDepartment of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
Sarah M NielsenInvitae Corporation, San Francisco, CA, USA.
Emily M RussellInvitae Corporation, San Francisco, CA, USA.
Edward D EsplinInvitae Corporation, San Francisco, CA, USA.
Hao WangDepartment of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
William B IsaacsDepartment of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: wisaacs1@jhmi.edu.
Emmanuel S AntonarakisDepartment of Medicine, Masonic Cancer Center, University of Minnesota, Minneapolis, MN, USA. Electronic address: anton401@umn.edu.
Jun LuoDepartment of Urology, James Buchanan Brady Urological Institute, Johns Hopkins University School of Medicine, Baltimore, MD, USA. Electronic address: jluo2@jhmi.edu.
Johns Hopkins University · USInvitae (United States) · USThe University of Texas Health Science Center at San Antonio · USUniversity of Minnesota · US

Funding

TISSUE CULTURE---COREP30CA054174 · NCI · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI Lei Zheng · 1991 to 2026
$59.1M
High Throughput DNA Sequencer: Illumina HiSeq 3000 SequencerS10OD021805 · OD · UNIVERSITY OF TEXAS HLTH SCIENCE CENTER · PI LAI, ZHAO · 2016 to 2016
$600k
NCI NIH HHS P30 CA054174NIH HHS S10 OD021805
6 · The paper itself

Abstract

backgroundRecent reports have uncovered a HOXB13 variant (X285K) predisposing to prostate cancer in men of West African ancestry. The clinical relevance and protein function associated with this inherited variant are unknown.

objectiveTo determine the clinical relevance of HOXB13 (X285K) in comparison with HOXB13 (G84E) and BRCA2 pathogenic/likely pathogenic (P/LP) variants, and to elucidate the oncogenic mechanisms of the X285K protein. DESIGN, SETTING, AND

participantsReal-world data were collected from 21,393 men with prostate cancer undergoing genetic testing from 2019 to 2022, and in vitro cell-line models were established for the evaluation of oncogenic functions associated with the X285K protein. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: Genetic testing results were compared among patient groups according to self-reported race/ethnicity, Gleason scores, and American Joint Committee on Cancer stages using the exact test. Oncogenic functions of X285K were evaluated by RNA sequencing, chromatin immunoprecipitation sequencing, and Western blot analyses. RESULTS AND LIMITATIONS: HOXB13 (X285K) was significantly enriched in self-reported Black (1.01%) versus White (0.01%) patients. We observed a trend of more aggressive disease in the HOXB13 (X285K) and BRCA2 P/LP carriers than in the HOXB13 (G84E) carriers. Replacement of the wild-type HOXB13 protein with the X285K protein resulted in a gain of an E2F/MYC signature, validated by the elevated expression of cyclin B1 and c-Myc, without affecting the androgen response signature. Elevated expression of cyclin B1 and c-Myc was explained by enhanced binding of the X285K protein to the promoters and enhancers of these genes. The limitations of the study are the lack of complete clinical outcome data for all patients studied and the use of a single cell line in the functional analysis.

conclusionsHOXB13 (X285K) is significantly enriched in self-reported Black patients, and X285K carriers detected in the real-world clinical setting have aggressive prostate cancer features similar to the BRCA2 carriers. Functional studies revealed a unique gain-of-function oncogenic mechanism of X285K protein in regulating E2F/MYC signatures. PATIENT SUMMARY: The HOXB13 (X285K) variant is clinically and functionally linked to aggressive prostate cancer, supporting genetic testing for X285K in Black men and early disease screening of carriers of this variant.

Indexed as

Homeodomain ProteinsProstatic NeoplasmsAgedBlack PeopleGain of Function MutationHumansMaleMiddle AgedHomeodomain ProteinsHOXB13 protein, humanGain of functionGermline variantHOXB13Prostate cancerX285K

Identifiers

PMID37806842
PMCPMC12848658
OpenAlexW4387396852

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.