Back to Search
Start Over
Myxoid smooth muscle neoplasia of the uterus: comprehensive analysis by next-generation sequencing and nucleic acid hybridization
- Source :
- Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc. 32(11)
- Publication Year :
- 2019
-
Abstract
- Uterine myxoid smooth muscle tumors, including myxoid leiomyosarcoma, are rare and their genomic profile has not been fully characterized. With the discovery of uterine sarcomas with ZC3H7B-BCOR fusion and BCOR internal tandem duplications, the differential diagnosis of myxoid smooth muscle lesions is expanding to include molecularly-defined tumors. Thus, we aimed to explore the genomic landscape of myxoid smooth muscle tumor using comprehensive tools. We performed whole exome next-generation sequencing and a pan-sarcoma RNA fusion assay in tumoral paraffin-embedded tissue from nine well-characterized uterine myxoid smooth muscle tumors (seven myxoid leiomyosarcomas and two myxoid smooth muscle tumors of unknown malignant potential). By immunohistochemistry, all tumors were strongly positive for smooth muscle markers and negative for BCOR staining; 4/6 expressed PLAG1. None of the tumors harbored known fusions including ZC3H7B-BCOR, TRPS1-PLAG1, and RAD51B-PLAG1. None harbored exon 15 BCOR internal tandem duplications; however, four tumors contained BCOR internal tandem duplications of unknown significance (mostly intronic). Mutational burden was low (median 3.8 mutations/megabase). DNA damage repair pathway gene mutations, including TP53 and BRCA2, were found. Copy number variation load, inferred from sequencing data, was variable with genomic indexes ranging from 2.2 to 74.7 (median 25.7), with higher indexes in myxoid leiomyosarcomas than myxoid smooth muscle tumors of unknown malignant potential. The absence of clear driver mutations suggests myxoid smooth muscle tumors to be genetically heterogeneous group of tumours and that other genetic (eg., undiscovered translocation) or epigenetic events drive the pathogenesis of uterine myxoid smooth muscle neoplasia.
- Subjects :
- 0301 basic medicine
Adult
Pathology
medicine.medical_specialty
Gene mutation
Biology
Pathology and Forensic Medicine
03 medical and health sciences
Exon
0302 clinical medicine
medicine
Humans
Copy-number variation
Exome
Smooth Muscle Tumor
Aged
Genetic heterogeneity
High-Throughput Nucleotide Sequencing
Nucleic Acid Hybridization
Middle Aged
030104 developmental biology
030220 oncology & carcinogenesis
Uterine Neoplasms
Immunohistochemistry
Female
Transcriptome
Myxoid Leiomyosarcoma
Subjects
Details
- ISSN :
- 15300285
- Volume :
- 32
- Issue :
- 11
- Database :
- OpenAIRE
- Journal :
- Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
- Accession number :
- edsair.doi.dedup.....79c518e1c3a3cd21b0c64ddd8dc2f5f7