2016
DOI: 10.1038/modpathol.2016.45
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Loss of H3K27 tri-methylation is a diagnostic marker for malignant peripheral nerve sheath tumors and an indicator for an inferior survival

Abstract: Malignant peripheral nerve sheath tumors (MPNSTs) are aggressive sarcomas that can show overlapping features with benign neurofibromas as well as high-grade sarcomas. Additional diagnostic markers are needed to aid in this often challenging differential diagnosis. Recently mutations in two critical components of the polycomb repressor 2 (PRC2) complex, SUZ12 and EED, were reported to occur specifically in MPNSTs while such mutations are absent in neurofibromas, both in the setting of neurofibromatosis (NF) and… Show more

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Cited by 181 publications
(191 citation statements)
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“…To examine the significance of the mast cell enrichment phenotype in human MPNST samples, we analyzed a tissue microarray of primary and locally recurrent MPNSTs with known NF1 status for c-Kit staining, a commonly used clinical marker of mast cells (31, 33). Mast cells were enriched in NF1-associated MPNSTs compared to sporadic MPNSTs (Figure 4F).…”
Section: Resultsmentioning
confidence: 99%
See 1 more Smart Citation
“…To examine the significance of the mast cell enrichment phenotype in human MPNST samples, we analyzed a tissue microarray of primary and locally recurrent MPNSTs with known NF1 status for c-Kit staining, a commonly used clinical marker of mast cells (31, 33). Mast cells were enriched in NF1-associated MPNSTs compared to sporadic MPNSTs (Figure 4F).…”
Section: Resultsmentioning
confidence: 99%
“…A human MPNST tissue microarray (TMA) was built using patient samples obtained under approval of the Institutional Review Board of The University of Texas MD Anderson Cancer Center as previously described (13, 31). An anonymized, full clinical database, including the neurofibromatosis status of each patient, was constructed.…”
Section: Methodsmentioning
confidence: 99%
“…In contrast, complete PRC2 inactivation occurs in malignant peripheral nerve sheath tumors through mutation of SUZ12 or EED 35–37 . It is likely that inactivation of PRC2 also occurs in other sarcomas in view of frequent H3K27me3 loss 38 . In pediatric high-grade gliomas (pHGG), point mutation of the K27 residue of H3.3 or H3.1 histone variants into methionine (H3K27M) lead to a global reduction of H3K27me3 39–41 .…”
Section: Discussionmentioning
confidence: 99%
“…At least four large studies have reported on the specificity and sensitivity of H3K27me3 loss in the diagnosis of MPNST. 3538 Most studies have found good specificity, with rare examples of H3K27me3 loss in other sarcomas. However, one large series noted H3K27me3 loss in a subsets of synovial sarcomas and fibrosarcomatous dermatofibrosarcoma protuberans (9/15 and 3/8, respectively), two close histologic mimics of MPNST.…”
Section: Mutations In Prc2 In Malignant Peripheral Nerve Sheath Tumormentioning
confidence: 99%
“…However, one large series noted H3K27me3 loss in a subsets of synovial sarcomas and fibrosarcomatous dermatofibrosarcoma protuberans (9/15 and 3/8, respectively), two close histologic mimics of MPNST. 35 The reported sensitivity values of H3K27me3 loss have been both more variable and less impressive (34—61%). In addition to its utility as a diagnostic marker, several series also found loss of H3K27me3 to have prognostic significance, as it was associated with aggressive disease.…”
Section: Mutations In Prc2 In Malignant Peripheral Nerve Sheath Tumormentioning
confidence: 99%