A rare case of malignant peritoneal mesothelioma with EWSR-ATF1 fusion transcription and unusual immunophenotype

Ajelero, Olawunmi; Zhang, Paul J.; Collingwood, R. G.; Fortuna, Danielle

doi:10.1016/j.ehpc.2021.200542

Cited by 2 publications

(4 citation statements)

References 18 publications

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“…ATF1 [15][16][17] have been reported. EWSR1::YY1 fusion was reported only in 2 cases of peritoneal mesothelioma, both in males in their sixties.…”

Section: Discussionmentioning

confidence: 99%

“…On the other hand, in children and young adults, rare cases of peritoneal mesotheliomas unrelated to asbestos exposure harboring recurrent gene fusions in ALK , 11–14 NTRK 14 and EWSR1/FUS::ATF1 15–17 have been reported. EWSR1::YY1 fusion was reported only in 2 cases of peritoneal mesothelioma, both in males in their sixties 18 .…”

Section: Discussionmentioning

confidence: 99%

“…Rare cases of peritoneal mesotheliomas, typically in children or young adults, harboring recurrent gene fusions in ALK 11–14 and EWSR1/FUS::ATF1 15–17 have been reported without associated asbestos exposure. Moreover, an EWSR1::YY1 fusion was reported in a single case study of 2 patients with peritoneal mesothelioma 18 .…”

Section: Introductionmentioning

confidence: 99%

“…[4][5][6][7][8] Additionally, genetic alterations in Hippo pathway genes [neurofibromatosis type 2/merlin (NF2), LATS1/2, RASSF1, SAV1], as well as SETD2, SETDB1, DDX3X, DDX51, TP53, CDKN2A, were also reported in a subset of malignant mesotheliomas. [4][5][6]9,10 Rare cases of peritoneal mesotheliomas, typically in children or young adults, harboring recurrent gene fusions in ALK [11][12][13][14] and EWSR1/FUS::ATF1 [15][16][17] have been reported without associated asbestos exposure. Moreover, an EWSR1::YY1 fusion was reported in a single case study of 2 patients with peritoneal mesothelioma.…”

Section: Introductionmentioning

confidence: 99%

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EWSR1::YY1 fusion positive peritoneal epithelioid mesothelioma harbors mesothelioma epigenetic signature: Report of 3 cases in support of an emerging entity

Dermawan

Torrence

Lee

et al. 2022

Genes Chromosomes & Cancer

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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.

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“…ATF1 [15][16][17] have been reported. EWSR1::YY1 fusion was reported only in 2 cases of peritoneal mesothelioma, both in males in their sixties.…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

EWSR1::YY1 fusion positive peritoneal epithelioid mesothelioma harbors mesothelioma epigenetic signature: Report of 3 cases in support of an emerging entity

Dermawan

Torrence

Lee

et al. 2022

Genes Chromosomes & Cancer

View full text Add to dashboard Cite

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Comprehensive genomic profiling of EWSR1/FUS::CREB translocation-associated tumors uncovers prognostically significant recurrent genetic alterations and methylation-transcriptional correlates

et al. 2022

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To elucidate the mechanisms underlying the divergent clinicopathologic spectrum of EWSR1/FUS - CREB translocation-associated tumors, we performed a comprehensive genomic analysis of fusion transcript variants, recurrent genetic alterations (mutations, copy number alterations), gene expression, and methylation profiles across a large cohort of tumor types. The distribution of the EWSR1 / FUS fusion partners – ATF1 , CREB1 , and CREM – and exon involvement was significantly different across different tumor types. Our targeted sequencing showed that secondary genetic events are associated with tumor type rather than fusion type. Of the 39 cases that underwent targeted NGS testing, 18 (46%) had secondary OncoKB mutations or copy number alterations (29 secondary genetic events in total), of which 15 (52%) were recurrent. Secondary recurrent, but mutually exclusive, TERT promoter and CDKN2A mutations were identified only in clear cell sarcoma (CCS) and associated with worse overall survival. CDKN2A/B homozygous deletions were recurrent in angiomatoid fibrous histiocytoma (AFH) and restricted to metastatic cases. mRNA upregulation of MITF , CDH19 , PARVB , and PFKP was found in CCS, compared to AFH, and correlated with a hypomethylated profile. In contrast, S100A4 and XAF1 were differentially upregulated and hypomethylated in AFH but not CCS. A sarcoma methylation classifier was able to accurately match 100% of CCS cases to the correct methylation class; however, it was suboptimal when applied to other histologies. In conclusion, our comprehensive genomic profiling of EWSR1/FUS - CREB translocation-associated tumors uncovered mostly histotype, rather than fusion-type associated correlations in transcript variants, prognostically significant secondary genetic alterations, and gene expression and methylation patterns.

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A rare case of malignant peritoneal mesothelioma with EWSR-ATF1 fusion transcription and unusual immunophenotype

Cited by 2 publications

References 18 publications

EWSR1::YY1 fusion positive peritoneal epithelioid mesothelioma harbors mesothelioma epigenetic signature: Report of 3 cases in support of an emerging entity

EWSR1::YY1 fusion positive peritoneal epithelioid mesothelioma harbors mesothelioma epigenetic signature: Report of 3 cases in support of an emerging entity

Comprehensive genomic profiling of EWSR1/FUS::CREB translocation-associated tumors uncovers prognostically significant recurrent genetic alterations and methylation-transcriptional correlates

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