Loss of H3K27me3 occurs in a large subset of embryonal rhabdomyosarcomas: Immunohistochemical and molecular analysis of 25 cases

Autor: Tess Tomassen, Caroline C. Hulsker, Lennart Kester, Laura S. Hiemcke-Jiwa, Hans H.M. Merks, Else Driehuis, Uta Flucke, Joost van Gorp, Max M. van Noesel, Bastiaan B J Tops, Roelof van Ewijk, Sheila E. J. Terwisscha van Scheltinga
Rok vydání: 2021
Předmět:
0301 basic medicine
Adult
Male
Pathology
medicine.medical_specialty
Adolescent
Malignant peripheral nerve sheath tumor
macromolecular substances
Rare cancers Radboud Institute for Molecular Life Sciences [Radboudumc 9]
Pathology and Forensic Medicine
Transcriptome
Diagnosis
Differential
Histones
03 medical and health sciences
Young Adult
0302 clinical medicine
All institutes and research themes of the Radboud University Medical Center
Rhabdomyosarcoma
medicine
Humans
Rhabdomyosarcoma
Embryonal
RNA-Seq
Neurofibromatosis
Child
Aged
biology
business.industry
Malignant triton tumor
Infant
Acetylation
Cell Differentiation
General Medicine
DNA Methylation
Middle Aged
medicine.disease
Immunohistochemistry
030104 developmental biology
Histone
Neurofibrosarcoma
030220 oncology & carcinogenesis
Child
Preschool
biology.protein
Female
Embryonal rhabdomyosarcoma
business
Zdroj: Annals of Diagnostic Pathology, 52
ISSN: 1532-8198
1092-9134
Popis: Loss of histone 3 lysine 27 trimethylation (H3K27me3) has been described as a diagnostic marker for malignant peripheral nerve sheath tumor (MPNST), also discriminating MPNST with rhabdomyoblastic differentiation (malignant Triton tumor) from rhabdomyosarcoma (RMS). We studied the immunohistochemical expression of H3K27me3 in embryonal RMSs (ERMSs), performed methylation profiling in order to support the diagnosis and RNA-sequencing for comparison of the transcriptome of H3K27me3-positive and -negative cases. Of the 25 ERMS patients, 17 were males and 8 were females with an age range from 1 to 67 years (median, 6 years). None were known with neurofibromatosis type 1. One patient had Li-Fraumeni syndrome. Tumor localization included paratesticular (n = 9), genitourinary (n = 6), head/neck (n = 5), retroperitoneal (n = 4) and lower arm (n = 1). Five MPNSTs served as reference group. All ERMS had classical features including a variable spindle cell component. Immunohistochemical loss (partial or complete) of H3K27me3 was detected in 18/25 cases (72%). Based on methylation profiling, 22/22 cases were classified as ERMS. Using RNA sequencing, the ERMS group (n = 14) had a distinct gene expression profile in contrast to MPNSTs, confirming that the H3K27me3 negative ERMS cases do not represent malignant Triton tumors. When comparing H3K27me3-negative and -positive ERMSs, gene set enrichment analysis revealed differential expression of genes related to histone acetylation and normal muscle function with H3K27me3 negative ERMSs being associated with acetylation. Conclusion: Loss of H3K27me3 frequently occurs in ERMSs and correlates with H3K27 acetylation. H3K27me3 is not a suitable marker to differentiate ERMS (with spindle cell features) from malignant Triton tumor.
Databáze: OpenAIRE
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