Denosumab treatment in aneurysmal bone cyst: Evaluation of nine cases

Kurucu, Nilgün; Akyüz, Canan; Ergen, Fatma Bilge; Yalçın, Bilgehan; Kösemehmetoğlu, Kemal; Ayvaz, Mehmet; Varan, Ali; Aydın, Burça; Kutluk, Tezer

doi:10.1002/pbc.26926

Cited by 76 publications

(84 citation statements)

References 26 publications

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“…Tumors can be locally aggressive and may recur in approximately 20% of cases, particularly in instances of incomplete surgical resection. Denosumab, a human monoclonal antibody against receptor activator of nuclear factor kappa‐B ligand (RANKL) that stimulates osteoclast differentiation, is emerging as a possible treatment for non‐resectable and recurrent ABCs …”

Section: Introductionmentioning

confidence: 99%

“…Denosumab, a human monoclonal antibody against receptor activator of nuclear factor kappa-B ligand (RANKL) that stimulates osteoclast differentiation, is emerging as a possible treatment for non-resectable and recurrent ABCs. 5 Primary ABCs are characterized by recurrent translocations involving the USP6 gene, which encodes the ubiquitin-specific peptidase 6 (USP6), on chromosome 17p13. 6,7 These rearrangements are restricted to the spindle cell population within ABCs.…”

Section: Introductionmentioning

confidence: 99%

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RNA sequencing identifies a novel USP9X‐USP6 promoter swap gene fusion in a primary aneurysmal bone cyst

Blackburn

Davila

Jackson

et al. 2019

Genes Chromosomes & Cancer

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Primary aneurysmal bone cyst (ABC) is a benign multiloculated cystic lesion of bone that is defined cytogenetically by USP6 gene rearrangements. Rearrangements involving USP6 are promoter swaps, usually generated by fusion of the noncoding upstream exons of different partner genes with exon 1 or 2 of USP6, thus leading to transcriptional upregulation of full‐length USP6 coding sequence. Testing for USP6 rearrangements is used diagnostically to distinguish it from secondary ABC and other giant cell‐rich primary bone tumors. In this report, we present a case of a 16‐year‐old male with a primary ABC of the left distal femur. USP6 break apart fluorescence in situ hybridization was positive for a rearrangement and conventional chromosome analysis identified a reciprocal X;17 translocation. In order to identify the putative USP6 fusion partner, we performed RNA sequencing and uncovered a novel USP9X‐USP6 promoter swap fusion. This result was confirmed by reverse transcription‐polymerase chain reaction (RT‐PCR) and by mate pair sequencing thus showing the utility of these alternative methodologies in identifying novel fusion candidates. Ubiquitin‐specific protease 9X (USP9X), like USP6, encodes a highly conserved substrate‐specific deubiquitylating enzyme. USP9X is highly expressed in a number of tissue types and acts as both an oncogene and tumor suppressor in several human cancers. We conclude that oncogenic activation of USP6 via USP9X promoter exchange represents a novel driver of primary ABC formation.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

RNA sequencing identifies a novel USP9X‐USP6 promoter swap gene fusion in a primary aneurysmal bone cyst

Blackburn

Davila

Jackson

et al. 2019

Genes Chromosomes & Cancer

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“…Other options include the use of cement, phenol, cryotherapy, and sclerotherapy. [24][25][26] Denosumab is a monoclonal antibody to RANKL that prevents it binding to its receptor RANK. 1,2,[18][19][20][21][22][23] This is usually associated with resolution of symptoms and an uneventful postoperative course; however, recurrences have been reported.…”

Section: Discussionmentioning

confidence: 99%

“…19,21,22 Denosumab has been reported to provide meaningful clinical and radiological improvement in aneurysmal bone cysts. [24][25][26] Denosumab is a monoclonal antibody to RANKL that prevents it binding to its receptor RANK. As a result, tumors lose the paracrine signaling stimulating giant cell differentiation and osteoclastic bone resorption.…”

Section: Discussionmentioning

confidence: 99%

Massive aneurysmal bone cyst of the skull base treated with denosumab

et al. 2018

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Background Aneurysmal bone cysts are rare, benign expansile tumors most commonly involving long bones and vertebrae in patients younger than age 20. Skull base involvement is rare. Aneurysmal bone cysts shares radiological and histological features with other bone tumors, posing a diagnostic challenge. Methods/Results We report the case of a 32‐year‐old man who presented with facial pain, epistaxis, and cranial neuropathies secondary to a massive tumor of the maxillary sinus and anterior skull base. The tumor was originally misdiagnosed as osteosarcoma. However, genomic analysis revealed a rearrangement in the USP6 gene, elucidating a diagnosis of primary aneurysmal bone cysts. The patient was treated with denosumab. Within 5 months, the patient was asymptomatic with CT showing ossification of the tumor. Conclusions This case highlights (1) the utility of genomic analysis in aggressive bone tumors when the diagnosis is unclear and (2) the effectiveness of denosumab as a treatment for aneurysmal bone cysts when surgical resection is unfavorable.

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“…It has been found that several types of bone lacerations involving osteoclastic giant cells such as; osteosarcoma, primary ABC, non-ossifying fibroma, chondroblastoma, brown tumor (hyperparathyroidism), giant cell reparative granuloma and the giant cell-rich type specifically exhibit much more distinction than GCTB. Recurrence in case of tumor posttreatment usually takes place after 3 years but, GCTs have shown late relapse such as 15 years of time span which occurs at the locus where surgical treatment was performed to eliminate the tumor [62,63].…”

Section: Giant Cell Tumor Of Bone (Gctb)mentioning

confidence: 99%

Role of cancer stem cells in the development of giant cell tumor of bone

et al. 2020

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The primary bone tumor is usually observed in adolescence age group which has been shown to be part of nearly 20% of the sarcomas known today. Giant cell tumor of bone (GCTB) can be benign as well as malignant tumor which exhibits localized dynamism and is usually associated with the end point of a long bone. Giant cell tumor (GCT) involves mononuclear stromal cells which proliferate at a high rate, multinucleated giant cells and stromal cells are equally present in this type of tumor. Cancer stem cells (CSCs) have been confirmed to play a potential role in the development of GCT. Cancer stem cell-based microRNAs have been shown to contribute to a greater extent in giant cell tumor of bone. CSCs and microRNAs present in the tumors specifically are a great concern today which need indepth knowledge as well as advanced techniques to treat the bone cancer effectively. In this review, we attempted to summarize the role played by cancer stem cells involving certain important molecules/factors such as; Mesenchymal Stem Cells (MSCs), miRNAs and signaling mechanism such as; mTOR/PI3K-AKT, towards the formation of giant cell tumor of bone, in order to get an insight regarding various effective strategies and research advancements to obtain adequate knowledge related to CSCs which may help to focus on highly effective treatment procedures for bone tumors.

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Denosumab treatment in aneurysmal bone cyst: Evaluation of nine cases

Cited by 76 publications

References 26 publications

RNA sequencing identifies a novel USP9X‐USP6 promoter swap gene fusion in a primary aneurysmal bone cyst

RNA sequencing identifies a novel USP9X‐USP6 promoter swap gene fusion in a primary aneurysmal bone cyst

Massive aneurysmal bone cyst of the skull base treated with denosumab

Role of cancer stem cells in the development of giant cell tumor of bone

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