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Nature Reviews. Cancer Oct 2020Epigenetic regulation is critical to physiological control of development, cell fate, cell proliferation, genomic integrity and, fundamentally, transcriptional... (Review)
Review
Epigenetic regulation is critical to physiological control of development, cell fate, cell proliferation, genomic integrity and, fundamentally, transcriptional regulation. This epigenetic control occurs at multiple levels including through DNA methylation, histone modification, nucleosome remodelling and modulation of the 3D chromatin structure. Alterations in genes that encode chromatin regulators are common among mesenchymal neoplasms, a collection of more than 160 tumour types including over 60 malignant variants (sarcomas) that have unique and varied genetic, biological and clinical characteristics. Herein, we review those sarcomas in which chromatin pathway alterations drive disease biology. Specifically, we emphasize examples of dysregulation of each level of epigenetic control though mechanisms that include alterations in metabolic enzymes that regulate DNA methylation and histone post-translational modifications, mutations in histone genes, subunit loss or fusions in chromatin remodelling and modifying complexes, and disruption of higher-order chromatin structure. Epigenetic mechanisms of tumorigenesis have been implicated in mesenchymal tumours ranging from chondroblastoma and giant cell tumour of bone to chondrosarcoma, malignant peripheral nerve sheath tumour, synovial sarcoma, epithelioid sarcoma and Ewing sarcoma - all diseases that present in a younger patient population than most cancers. Finally, we review current and potential future approaches for the development of sarcoma therapies based on this emerging understanding of chromatin dysregulation.
Topics: Animals; Biomarkers, Tumor; Cell Transformation, Neoplastic; Chromatin; Chromatin Assembly and Disassembly; DNA Methylation; Epigenesis, Genetic; Epigenomics; Gene Expression Regulation, Neoplastic; Genetic Association Studies; Genetic Predisposition to Disease; Humans; Sarcoma
PubMed: 32782366
DOI: 10.1038/s41568-020-0288-4 -
Archives of Pathology & Laboratory... Jan 2020Chondroblastoma-like osteosarcoma is an exceedingly rare variant of osteosarcoma, with 22 cases reported in the English-language literature. The tumor is slightly more... (Review)
Review
CONTEXT.—
Chondroblastoma-like osteosarcoma is an exceedingly rare variant of osteosarcoma, with 22 cases reported in the English-language literature. The tumor is slightly more common in males, with a broad age range (from childhood to elderly). The most commonly involved bones are the metatarsus and tibia, followed by the femur. Most tumors have malignant or worrisome radiographic findings. Prognosis is variable, depending on the presence or absence of lung metastases, local recurrence, and probably tumor location. Histologically, chondroblastoma-like osteosarcoma is characterized by monotonous, minimally to moderately atypical rounded cells with ovoid nuclei resembling chondroblastoma, and abnormal osteoid deposition with destruction of the bone.
OBJECTIVE.—
To review the clinical, radiographic, and histopathologic features of chondroblastoma-like osteosarcoma.
DATA SOURCES.—
PubMed-published chondroblastoma-like osteosarcoma cases in the English-language literature.
CONCLUSIONS.—
Although exceedingly rare, chondroblastoma-like osteosarcoma should be considered in the differential diagnosis of chondroblastoma, especially in the presence of radiologic findings suggestive of an aggressive lesion.
Topics: Bone Neoplasms; Chondroblastoma; Diagnosis, Differential; Humans; Osteosarcoma
PubMed: 31389716
DOI: 10.5858/arpa.2019-0191-RA -
Archives of Pathology & Laboratory... Jun 2017Chondroblastoma is a rare primary bone tumor of young people that typically arises in the ends of the long bones. Radiologic investigations show a small, circumscribed,... (Review)
Review
Chondroblastoma is a rare primary bone tumor of young people that typically arises in the ends of the long bones. Radiologic investigations show a small, circumscribed, lytic lesion. The tumor is characterized histologically by the proliferation of chondroblasts along with areas of mature cartilage, giant cells, and occasionally, secondary aneurysmal bone cyst formation. Chondroblastoma, however, may also present with atypical features, such as prominent hemosiderin deposition, numerous giant cells, or the presence of a large aneurysmal bone cyst component. Malignant entities such as clear cell chondrosarcoma and chondroblastic osteosarcoma must also be considered. Recently, immunohistochemical stains such as DOG1 and SOX9 have been described in chondroblastoma, and K36M mutations in either the H3F3A or H3F3B genes have also been identified. While generally regarded as a benign entity, chondroblastoma manifests an intermediate type of behavior, given its ability to recur locally, and rarely, metastasize.
Topics: Amino Acid Substitution; Anoctamin-1; Bone Neoplasms; Bone and Bones; Chloride Channels; Chondroblastoma; Chondrosarcoma; Diagnosis, Differential; Histones; Humans; Mutation; Neoplasm Proteins; Neoplasm Recurrence, Local; Osteosarcoma; SOX9 Transcription Factor
PubMed: 28557595
DOI: 10.5858/arpa.2016-0281-RS -
Indian Journal of Otolaryngology and... Dec 2022Mass lesions of the larynx are one of the most common clinical entity which we come across in routine otorhinolaryngology and head neck practice with varied...
Mass lesions of the larynx are one of the most common clinical entity which we come across in routine otorhinolaryngology and head neck practice with varied symptomatology. Among all the mass lesions of the larynx, Epithelial neoplasms constitute up to 97%. Mesenchymal tumours of the larynx constitute only 0.3-1.0% of all the laryngeal tumors. Abundance of cartilage structures in the larynx made it a spot for mesenchymal tumors [chondromas and chandrosacrcomas]. The spectrum of mesenchymal neoplasms can vary from chondromas, chondroblastoma to chondrosarcoma. Here we want to share our experience of a mesenchymal tumour of the larynx. This case is reported for the rarity and ambiguity in diagnosis. Though these are slow-growing tumours with an early presentation, in our case, the patient had a supportive tracheostomy without definitive treatment for more than 2 years. We managed this patient by excising the mass by lateral pharyngotomy with the preservation of larynx followed by successful Decannulation in 20 days.
PubMed: 36742506
DOI: 10.1007/s12070-020-02308-8 -
Current Pharmacology Reports 2018Histone modifications are one form of epigenetic information that relate closely to gene regulation. Aberrant histone methylation caused by alteration in... (Review)
Review
Histone modifications are one form of epigenetic information that relate closely to gene regulation. Aberrant histone methylation caused by alteration in chromatin-modifying enzymes has long been implicated in cancers. More recently, recurrent histone mutations have been identified in multiple cancers and have been shown to impede histone methylation. All three histone mutations (H3K27M, H3K36M, and H3G34V/R) identified result in amino acid substitution at/near a lysine residue that is a target of methylation. In the cases of H3K27M and H3K36M, found in pediatric DIPG (diffuse intrinsic pontine glioma) and chondroblastoma respectively, expression of the mutant histone leads to global reduction of histone methylation at the respective lysine residue. These mutant histones are termed "oncohistones" because their expression reprograms the epigenome and shapes an oncogenic transcriptome. Dissecting the mechanism of H3K27M-driven oncogenesis has led to the discovery of promising therapeutic targets in pediatric DIPG. The purpose of this review is to summarize the work done on identifying and dissecting the oncogenic properties of histone H3 mutations.
PubMed: 30101054
DOI: 10.1007/s40495-018-0141-6 -
World Journal of Surgical Oncology Apr 2015The patella is an uncommon location for cancerous occurrence and development. The majority of tumors of the patella are benign, with a significant incidence of giant... (Review)
Review
The patella is an uncommon location for cancerous occurrence and development. The majority of tumors of the patella are benign, with a significant incidence of giant cell tumors and chondroblastoma. With the development of modern diagnostic technologies, there appear however many other histological types which raise challenges of diagnosis and treatment. In this article, we review the reported histological types of primary patellar tumors. Specifically, epidemiology, symptomatology, imageology, histopathology, and treatment options for these histological lesions will be discussed, respectively. As there is an increasing focus on the diagnosis and the treatment of these lesions, the availability of the integrated information about primary patellar tumors becomes more significant.
Topics: Bone Neoplasms; Humans; Patella
PubMed: 25906772
DOI: 10.1186/s12957-015-0573-y -
Journal of Molecular Medicine (Berlin,... Apr 2015Rare conditions are sometimes ignored in biomedical research because of difficulties in obtaining specimens and limited interest from fund raisers. However, the study of... (Review)
Review
Rare conditions are sometimes ignored in biomedical research because of difficulties in obtaining specimens and limited interest from fund raisers. However, the study of rare diseases such as unusual cancers has again and again led to breakthroughs in our understanding of more common diseases. It is therefore unsurprising that with the development and accessibility of next-generation sequencing, much has been learnt from studying cancers that are rare and in particular those with uniform biological and clinical behavior. Herein, we describe how shotgun sequencing of cancers such as granulosa cell tumor, endometrial stromal sarcoma, epithelioid hemangioendothelioma, ameloblastoma, small-cell carcinoma of the ovary, clear-cell carcinoma of the ovary, nonepithelial ovarian tumors, chondroblastoma, and giant cell tumor of the bone has led to rapidly translatable discoveries in diagnostics and tumor taxonomies, as well as providing insights into cancer biology.
Topics: Animals; Genomics; High-Throughput Nucleotide Sequencing; Humans; Mutation; Neoplasms
PubMed: 25676695
DOI: 10.1007/s00109-015-1260-8