EWSR1::YY1 fusion positive peritoneal epithelioid mesothelioma harbors mesothelioma epigenetic signature: Report of 3 cases in support of an emerging entity.
EWSR1
YY1
gene fusion
methylation profiling
peritoneal mesothelioma
Journal
Genes, chromosomes & cancer
ISSN: 1098-2264
Titre abrégé: Genes Chromosomes Cancer
Pays: United States
ID NLM: 9007329
Informations de publication
Date de publication:
10 2022
10 2022
Historique:
revised:
26
05
2022
received:
20
04
2022
accepted:
29
05
2022
pubmed:
7
6
2022
medline:
6
8
2022
entrez:
6
6
2022
Statut:
ppublish
Résumé
Mesothelioma is a rare, aggressive malignant neoplasm of mesothelial origin. A small subset of peritoneal mesothelioma is driven by recurrent gene fusions, mostly EWSR1/FUS::ATF1 fusions, with predilection for young adults. To date, only two cases of mesothelioma harboring EWSR1::YY1 fusions have been described. We present three additional cases of EWSR1::YY1-fused peritoneal mesotheliomas, two localized and one diffuse, all occurring in the peritoneum of middle-aged adults (2 females and 1 male), and discovered incidentally by imaging or during surgery performed for unrelated reasons. None presented with symptoms or had a known history of asbestos exposure. All three cases were cellular epithelioid neoplasms with heterogeneous architectural patterns comprising mostly solid nests and sheets with variably papillary and trabecular areas against collagenous stroma. Cytologically, the cells were monomorphic, polygonal, epithelioid cells with dense eosinophilic cytoplasm and centrally located nuclei. Overt mitotic activity or tumor necrosis was absent. All cases showed strong diffuse immunoreactivity for pancytokeratin, CK7, and nuclear WT1, patchy to negative calretinin, retained BAP1 expression, and were negative for Ber-EP4 and MOC31. RNA-sequencing confirmed in-frame gene fusion transcripts involving EWSR1 exon 7/8 and YY1 exon 2/3. By unsupervised clustering analysis, the methylation profiles of EWSR1::YY1-fused mesotheliomas clustered similarly with EWSR1/FUS::ATF1-fused mesotheliomas and conventional mesotheliomas, suggesting a mesothelioma epigenetic signature. All three patients underwent surgical resection or cytoreductive surgery of the masses. On follow-up imaging, no recurrence or progression of disease was identified. Our findings suggest that EWSR1::YY1-fusion defines a small subset of peritoneal epithelioid mesothelioma in middle-aged adults without history of asbestos exposure.
Identifiants
pubmed: 35665561
doi: 10.1002/gcc.23074
pmc: PMC9811235
mid: NIHMS1858858
doi:
Substances chimiques
Biomarkers, Tumor
0
EWSR1 protein, human
0
RNA-Binding Protein EWS
0
YY1 Transcription Factor
0
YY1 protein, human
0
Types de publication
Case Reports
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
592-602Subventions
Organisme : NCI NIH HHS
ID : P30 CA008748
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA140146
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA217694
Pays : United States
Informations de copyright
© 2022 Wiley Periodicals LLC.
Références
Arch Pathol Lab Med. 2018 Feb;142(2):236-242
pubmed: 29048219
J Thorac Oncol. 2015 May;10(5):844-851
pubmed: 25902174
Exp Mol Med. 2017 Apr 28;49(4):e322
pubmed: 28450738
Mod Pathol. 2020 Nov;33(11):2269-2279
pubmed: 32504035
Int J Cancer. 2018 Aug 1;143(3):460-465
pubmed: 29322514
Nat Commun. 2021 Jan 21;12(1):498
pubmed: 33479225
Nat Genet. 2016 Apr;48(4):407-16
pubmed: 26928227
Am J Surg Pathol. 2020 Mar;44(3):293-304
pubmed: 31876584
Nat Genet. 2011 Aug 28;43(10):1022-5
pubmed: 21874000
J Thorac Oncol. 2020 Mar;15(3):457-461
pubmed: 31783178
Pediatr Dev Pathol. 2021 Nov-Dec;24(6):570-574
pubmed: 34121509
Bioinformatics. 2014 May 15;30(10):1363-9
pubmed: 24478339
Biochim Biophys Acta Mol Basis Dis. 2019 Jul 1;1865(7):1938-1945
pubmed: 30481590
Clin Cancer Res. 2017 Jun 15;23(12):3191-3202
pubmed: 28003305
Biostatistics. 2007 Jan;8(1):118-27
pubmed: 16632515
Hum Pathol. 2013 Jan;44(1):1-19
pubmed: 22963903
Mod Pathol. 2019 May;32(5):609-620
pubmed: 30459475
Am J Surg Pathol. 2018 Feb;42(2):256-263
pubmed: 29076876
Genes Chromosomes Cancer. 2013 Aug;52(8):733-40
pubmed: 23630070
J Mol Diagn. 2020 Mar;22(3):368-375
pubmed: 31881335
J Thorac Oncol. 2022 Mar;17(3):455-460
pubmed: 34648949
Hum Pathol. 2016 May;51:9-15
pubmed: 27067777
BMC Bioinformatics. 2010 Nov 30;11:587
pubmed: 21118553
Diagnostics (Basel). 2021 Jun 15;11(6):
pubmed: 34203801
J Thorac Oncol. 2019 Nov;14(11):1989-1994
pubmed: 31323388
Am J Surg Pathol. 2017 Jul;41(7):980-988
pubmed: 28505004
Am J Clin Pathol. 2005 May;123(5):724-37
pubmed: 15981812
Am J Surg Pathol. 2021 May 1;45(5):653-661
pubmed: 33399341
J Mol Diagn. 2021 Jul;23(7):834-846
pubmed: 33887463
Cancer Discov. 2018 Dec;8(12):1548-1565
pubmed: 30322867
Am J Surg Pathol. 1995 Oct;19(10):1124-37
pubmed: 7573671
Nat Genet. 2013 Oct;45(10):1113-20
pubmed: 24071849
Pathology. 2013 Aug;45(5):464-73
pubmed: 23846294
Histopathology. 2014 Jan;64(1):134-50
pubmed: 24320889
J Transl Med. 2015 Apr 16;13:122
pubmed: 25889843
Ann Transl Med. 2017 Jun;5(11):236
pubmed: 28706904
Lung Cancer. 2020 Aug;146:154-159
pubmed: 32540558
Mod Pathol. 2017 Feb;30(2):246-254
pubmed: 27813512
Am J Surg Pathol. 2016 Jan;40(1):120-6
pubmed: 26448191
Front Cell Dev Biol. 2020 Sep 30;8:592164
pubmed: 33102493
JAMA Oncol. 2018 Feb 01;4(2):235-238
pubmed: 28910456
J Thorac Oncol. 2017 Apr;12(4):724-733
pubmed: 28034829
Mod Pathol. 2016 Jan;29(1):14-24
pubmed: 26493618
Mod Pathol. 2021 Feb;34(2):380-395
pubmed: 33060816
Oncogene. 2006 Feb 23;25(8):1125-42
pubmed: 16314846
Hum Pathol. 2018 Sep;79:168-176
pubmed: 29763720
J Clin Oncol. 2018 Oct 1;36(28):2863-2871
pubmed: 30113886