Ductal and acinar components of mixed prostatic adenocarcinoma frequently have a common clonal origin.
clonality
ductal adenocarcinoma
genetics
prostate cancer
Journal
The Prostate
ISSN: 1097-0045
Titre abrégé: Prostate
Pays: United States
ID NLM: 8101368
Informations de publication
Date de publication:
04 2022
04 2022
Historique:
revised:
08
12
2021
received:
17
09
2021
accepted:
30
12
2021
pubmed:
21
1
2022
medline:
15
4
2022
entrez:
20
1
2022
Statut:
ppublish
Résumé
Ductal adenocarcinoma (DA) is an aggressive subtype of prostate cancer. It is most commonly seen in mixed tumors together with conventional acinar adenocarcinoma (AA). The genetic profile of DA and its clonal origin is not fully characterized. To investigate whether DA represents a distinct genetic subtype and to investigate the somatic relationship between the ductal and acinar components of mixed cancers. In 17 radical prostatectomy specimens ductal and acinar tumor components from the same tumor foci were dissected. DNA was extracted and genomic sequencing performed. After exclusion of two cases with low cell yield, 15 paired samples remained for analysis. In 12 of 15 cases a common somatic denominator was identified, while three cases had clonally separate components. In DA, TMPRSS2-ERG gene fusions were detected in 47% (7/15), clonal FOXA1 alterations in 33% (5/15) and SPOP alterations in 27% (4/15) of cases. In one case KIAA1549-BRAF fusion was identified. Genome doubling events, resulting in an increased ploidy, were identified in the DA in 53% (8/15) of cases, but not seen in any AA. PTEN and CTNNB1 alterations were enriched in DA (6/15) but not seen in any AA. No cancers showed microsatellite instability or high tumor mutation burden. Ductal and acinar prostate adenocarcinoma components of mixed tumors most often share the same origin and are clonally related. DA components in mixed tumor often exhibit genome doubling events resulting in aneuploidy, consistent with the aggressive nature of high grade prostate cancer.
Sections du résumé
BACKGROUND
Ductal adenocarcinoma (DA) is an aggressive subtype of prostate cancer. It is most commonly seen in mixed tumors together with conventional acinar adenocarcinoma (AA). The genetic profile of DA and its clonal origin is not fully characterized.
OBJECTIVE
To investigate whether DA represents a distinct genetic subtype and to investigate the somatic relationship between the ductal and acinar components of mixed cancers.
DESIGN, SETTING, AND PARTICIPANTS
In 17 radical prostatectomy specimens ductal and acinar tumor components from the same tumor foci were dissected. DNA was extracted and genomic sequencing performed. After exclusion of two cases with low cell yield, 15 paired samples remained for analysis.
RESULTS
In 12 of 15 cases a common somatic denominator was identified, while three cases had clonally separate components. In DA, TMPRSS2-ERG gene fusions were detected in 47% (7/15), clonal FOXA1 alterations in 33% (5/15) and SPOP alterations in 27% (4/15) of cases. In one case KIAA1549-BRAF fusion was identified. Genome doubling events, resulting in an increased ploidy, were identified in the DA in 53% (8/15) of cases, but not seen in any AA. PTEN and CTNNB1 alterations were enriched in DA (6/15) but not seen in any AA. No cancers showed microsatellite instability or high tumor mutation burden.
CONCLUSIONS
Ductal and acinar prostate adenocarcinoma components of mixed tumors most often share the same origin and are clonally related. DA components in mixed tumor often exhibit genome doubling events resulting in aneuploidy, consistent with the aggressive nature of high grade prostate cancer.
Identifiants
pubmed: 35049068
doi: 10.1002/pros.24304
pmc: PMC9306900
doi:
Substances chimiques
Nuclear Proteins
0
Repressor Proteins
0
SPOP protein, human
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
576-583Informations de copyright
© 2022 The Authors. The Prostate published by Wiley Periodicals LLC.
Références
Eur Urol Focus. 2019 May;5(3):433-442
pubmed: 29229583
Nature. 2021 Feb;590(7846):E53
pubmed: 33536625
Nat Genet. 2018 Aug;50(8):1189-1195
pubmed: 30013179
Pathology. 2016 Aug;48(5):398-405
pubmed: 27321992
Nat Commun. 2015 Dec 04;6:8971
pubmed: 26634437
Prostate. 2015 Oct;75(14):1610-9
pubmed: 26178158
Mod Pathol. 2009 Mar;22(3):359-65
pubmed: 19151660
Genet Med. 2019 Apr;21(4):972-981
pubmed: 30287923
Am J Surg Pathol. 1999 Jul;23(7):781-5
pubmed: 10403300
Oncotarget. 2016 Dec 13;7(50):82504-82510
pubmed: 27756888
Cell. 2015 Nov 5;163(4):1011-25
pubmed: 26544944
Cancer. 1967 Oct;20(10):1715-22
pubmed: 4168340
Am J Surg Pathol. 2005 Sep;29(9):1228-42
pubmed: 16096414
Source Code Biol Med. 2016 Dec 15;11:13
pubmed: 27999612
Prostate. 2022 Apr;82(5):576-583
pubmed: 35049068
Cell. 2018 Jun 14;173(7):1770-1782.e14
pubmed: 29906450
Hum Pathol. 2017 Nov;69:1-7
pubmed: 28457729
Eur Urol. 2013 Feb;63(2):347-53
pubmed: 22502944
Virchows Arch. 2013 Apr;462(4):429-36
pubmed: 23443941
Nat Commun. 2019 Nov 20;10(1):5251
pubmed: 31748536
Genome Med. 2018 Nov 21;10(1):85
pubmed: 30458854
Nat Genet. 2015 Apr;47(4):367-372
pubmed: 25730763
APMIS. 2019 Aug;127(8):554-560
pubmed: 31127651
Eur Urol. 2021 Feb;79(2):298-306
pubmed: 33279304
Nat Biotechnol. 2011 Jan;29(1):24-6
pubmed: 21221095
JCO Precis Oncol. 2019;3:
pubmed: 31123724
Eur Urol. 2016 Jul;70(1):106-119
pubmed: 26996659
Prostate. 2019 Jun;79(8):920-928
pubmed: 30908670
Eur Urol. 2015 May;67(5):819-22
pubmed: 25246081
Hum Pathol. 2010 Feb;41(2):281-5
pubmed: 20004936