A copy number gain on 18q present in primary prostate tumors is associated with metastatic outcome.
Array CGH
Chromosome 18
MALT1
Outcome
Prostate cancer
Journal
Urologic oncology
ISSN: 1873-2496
Titre abrégé: Urol Oncol
Pays: United States
ID NLM: 9805460
Informations de publication
Date de publication:
12 2020
12 2020
Historique:
received:
13
02
2020
revised:
11
06
2020
accepted:
15
06
2020
pubmed:
16
7
2020
medline:
6
8
2021
entrez:
16
7
2020
Statut:
ppublish
Résumé
Most prostate cancers (CaPs) grow slowly and remain indolent, yet some become aggressive and metastasize. Clinical decision-making requires prognostic markers that can be utilized at the time of diagnosis to identify aggressive tumors. Previous studies have shown a correlation between genomic alterations on the long arm of chromosome 18 (18q) and metastatic CaP. The goal of this study was to comprehensively profile copy number alterations found on 18q in prostate tumors with varying outcomes to identify putative biomarkers associated with more aggressive disease METHODS: A custom comparative genomic hybridization array was created composed of high-density tiling of 18q sequences. Primary prostate tumor tissues were gathered from men who underwent radical prostatectomy and were categorized based on the patient's long-term clinical outcome as either metastatic disease (MET) or no evidence of disease (NED). DNA was isolated from formalin-fixed, paraffin-embedded prostatectomy tumor tissues, and analyzed for copy number variations (CNVs). Protein levels of genes found within the region of CNVs were analyzed using immunohistochemistry. Thirty-Four primary prostate tumors were analyzed: 17 NEDs and 17 METs. Two significant regions of copy number gains were found on 18q associated with outcome. One gain located at 18q11.2 was found exclusively in NED outcome tumors while another gain, located at 18q21.31, was found exclusively in MET outcome tumors (P -value< 0.0076). Immunohistochemistry analysis of protein levels showed more protein associated with copy number gain in the MET samples vs. those without the gain as indicated by H-scores of 184.7 and 121.0 respectively. The latter of these CNVs represent a putative biomarker for aggressive disease and highlights a putative metastasis promoting gene. Further study of known connections to CaP suggests that the paracaspase MALT1 is the most likely target of the copy number gain and represents a potential therapeutic target. Future studies would be of interest to determine MALT1's role in aggressive CaP and the ability of this CNV region to differentiate CaP that will eventually metastasize.
Sections du résumé
BACKGROUND
Most prostate cancers (CaPs) grow slowly and remain indolent, yet some become aggressive and metastasize. Clinical decision-making requires prognostic markers that can be utilized at the time of diagnosis to identify aggressive tumors. Previous studies have shown a correlation between genomic alterations on the long arm of chromosome 18 (18q) and metastatic CaP.
OBJECTIVE
The goal of this study was to comprehensively profile copy number alterations found on 18q in prostate tumors with varying outcomes to identify putative biomarkers associated with more aggressive disease METHODS: A custom comparative genomic hybridization array was created composed of high-density tiling of 18q sequences. Primary prostate tumor tissues were gathered from men who underwent radical prostatectomy and were categorized based on the patient's long-term clinical outcome as either metastatic disease (MET) or no evidence of disease (NED). DNA was isolated from formalin-fixed, paraffin-embedded prostatectomy tumor tissues, and analyzed for copy number variations (CNVs). Protein levels of genes found within the region of CNVs were analyzed using immunohistochemistry.
RESULTS
Thirty-Four primary prostate tumors were analyzed: 17 NEDs and 17 METs. Two significant regions of copy number gains were found on 18q associated with outcome. One gain located at 18q11.2 was found exclusively in NED outcome tumors while another gain, located at 18q21.31, was found exclusively in MET outcome tumors (P -value< 0.0076). Immunohistochemistry analysis of protein levels showed more protein associated with copy number gain in the MET samples vs. those without the gain as indicated by H-scores of 184.7 and 121.0 respectively.
CONCLUSIONS
The latter of these CNVs represent a putative biomarker for aggressive disease and highlights a putative metastasis promoting gene. Further study of known connections to CaP suggests that the paracaspase MALT1 is the most likely target of the copy number gain and represents a potential therapeutic target. Future studies would be of interest to determine MALT1's role in aggressive CaP and the ability of this CNV region to differentiate CaP that will eventually metastasize.
Identifiants
pubmed: 32665124
pii: S1078-1439(20)30285-4
doi: 10.1016/j.urolonc.2020.06.015
pmc: PMC7996004
mid: NIHMS1675010
pii:
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
932.e1-932.e7Subventions
Organisme : NIGMS NIH HHS
ID : K12 GM111726
Pays : United States
Organisme : NCI NIH HHS
ID : P30 CA054174
Pays : United States
Organisme : NCI NIH HHS
ID : U01 CA086402
Pays : United States
Informations de copyright
Copyright © 2020 Elsevier Inc. All rights reserved.
Références
Cell. 2015 May 21;161(5):1215-1228
pubmed: 26000489
PLoS One. 2013;8(4):e60983
pubmed: 23577181
Cancer Surv. 1995;24:3-17
pubmed: 7553661
BMC Med Genomics. 2010 Mar 16;3:8
pubmed: 20233430
Cancer Res. 2018 Mar 1;78(5):1225-1240
pubmed: 29259013
Cancer Genet. 2014 Oct-Dec;207(10-12):474-88
pubmed: 25434580
PLoS One. 2013 Nov 28;8(11):e81514
pubmed: 24312311
Pancreas. 2004 Apr;28(3):311-6
pubmed: 15084978
Anticancer Res. 2012 Jun;32(6):2301-8
pubmed: 22641666
BMC Med Genomics. 2009 Apr 24;2:18
pubmed: 19393097
Curr Opin Endocrinol Diabetes Obes. 2013 Jun;20(3):204-9
pubmed: 23609043
Oncotarget. 2016 Dec 27;7(52):86339-86349
pubmed: 27861151
Hum Pathol. 1996 Jul;27(7):720-7
pubmed: 8698318
Int J Cancer. 2000 Mar 1;85(5):654-8
pubmed: 10699945
J Cancer. 2013 May 09;4(5):350-7
pubmed: 23781281
Genes Chromosomes Cancer. 1997 Oct;20(2):140-7
pubmed: 9331564
Nat Med. 2016 Mar;22(3):298-305
pubmed: 26855148