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Single-cell transcriptome analysis reveals T-cell exhaustion in denosumab-treated giant cell tumor of bone

ABSTRACT: Single-cell transcriptome analysis reveals T-cell exhaustion in denosumab-treated giant cell tumor of bone

PROVIDER: PRJNA875075 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21350400_1.fastq.gz	Fastqsanger.gz
	SRR21350400_2.fastq.gz	Fastqsanger.gz
	SRR21350401_1.fastq.gz	Fastqsanger.gz
	SRR21350401_2.fastq.gz	Fastqsanger.gz
	SRR21350402_1.fastq.gz	Fastqsanger.gz

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Project description:Giant cell granulomas of the jaws often occur sporadically as single central or peripheral lesions. They are characterized by KRAS, FGFR1, or TRPV4 somatic mutations, the latter occurring exclusively in the central form. Less commonly, multiple giant cell lesions can develop in the context of syndromes such as cherubism, which is an autosomal dominant bone disease. Morphologically, giant cell granulomas can closely resemble other giant cell-rich lesions such as non-ossifying fibroma and aneurysmal bone cyst, and to a minor extent giant cell tumour of bone and chondroblastoma. The epigenetic basis of these giant cell-rich tumours is unclear and, recently, DNA methylation profile has been shown to be clinically useful for the diagnosis of other tumour types, including brain tumours as well as bone and soft tissue sarcomas. Therefore, we aimed to assess the DNA methylation profile of central and peripheral sporadic giant cell granulomas of the jaws and cherubism to test whether DNA methylation patterns can help to distinguish these entities. Additionally, we further compared the DNA methylation profile of these lesions with those of other giant cell-rich mimics to investigate if the microscopic similarities extend to the epigenetic level. Our results showed that central and peripheral sporadic giant cell granulomas of the jaws and cherubism share a related DNA methylation pattern with that of peripheral sporadic giant cell granulomas and cherubism appearing slightly distinct, while central sporadic giant cell granulomas show overlap with both of the former. Non-ossifying fibroma, aneurysmal bone cyst, giant cell tumour of bone, and chondroblastoma, on the other hand, have distinct methylation patterns. Therefore, DNA methylation profiling is currently not capable of clearly distinguishing sporadic and cherubism-associated giant cell lesions of the jaws. Conversely, it could discriminate sporadic giant cell granulomas from their giant cell-rich mimics.

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Single-cell transcriptome analysis reveals T-cell exhaustion in denosumab-treated giant cell tumor of bone

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