Absence of H3F3A mutation in a subset of malignant giant cell tumor of bone

Yoshida, Kenichi; Nakano, Yoshiko; Honda‐Kitahara, Mai; Wakai, Susumu; Motoi, Toru; Ogura, Koichi; Sano, Naoki; Shibata, Tatsuhiro; Okuma, Tomotake; Iwata, Shintaro; Kawai, Akira; Ichimura, Koichi; Yoshida, Akihiko

doi:10.1038/s41379-019-0318-5

Cited by 40 publications

(36 citation statements)

References 30 publications

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“…Giant cell tumor of bone (GCTB) is an intermediate malignant osteoclastogenic stromal tumor with a broad biological spectrum [ 1 ]. Genetically, GCTB is characterized by specific mutations in the H3F3A gene, which encodes histone H3.3 [ 2 ]. Typically, this tumor involves the metaphyseal-epiphyseal region of long bones [ 3 ].…”

Section: Introductionmentioning

confidence: 99%

Late Local Recurrence of Bone Giant Cell Tumors Associated with an Increased Risk for Malignant Transformation

Tsukamoto

Righi

Mavrogenis

et al. 2021

Cancers

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In giant cell tumor of bone (GCTB), an intermediate malignant bone tumor, approximately 4% of all cases undergo malignant transformation. Accordingly, we analyzed risk factors for malignant transformation of GCTB treated without radiotherapy. We retrospectively reviewed medical records of 530 patients with GCTB of the extremities, admitted and treated at two institutions between January 1980 and December 2019. Overall, 4 patients with primary malignant GCTB, 4 patients with missing data, 3 patients with a history of radiotherapy, 22 patients with a follow-up of less than 6 months, and 36 patients who received denosumab were excluded. Accordingly, 461 patients were included for further analysis. Malignant transformation was observed in 15 of 461 patients (3.3%) at a median follow-up period of 192 months. The median follow-up duration was 89.4 months. Multivariate analysis revealed that local recurrence was an independent prognostic factor for unfavorable malignant transformation (Hazard ratio [HR], 11.33; 95% confidence interval [CI] 2.33–55.13; p = 0.003 for once versus none and HR, 11.24; 95% CI, 1.76–71.96; and p = 0.011 for twice or more versus none). The interval between the last surgery to local recurrence and malignant transformation was longer than that to local recurrence of benign GCTB, with a median of 15.2 years (interquartile range [IQR], 5.2–25.4) versus 1.3 months (IQR, 0.8–2.6), respectively (p < 0.001). Late local recurrence of GCTB is associated with a higher risk of malignant transformation.

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Section: Introductionmentioning

confidence: 99%

Late Local Recurrence of Bone Giant Cell Tumors Associated with an Increased Risk for Malignant Transformation

Tsukamoto

Righi

Mavrogenis

et al. 2021

Cancers

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“…The existing literature on GCTB is mostly comprised of genetic and genomic studies and clinical case reports ( 68 , 69 ). These studies provide a basis for understanding the current treatment strategies for GCTB.…”

Section: Discussionmentioning

confidence: 99%

Single-Cell RNA Sequencing Reveals the Migration of Osteoclasts in Giant Cell Tumor of Bone

Feng

Jiang

et al. 2021

Front. Oncol.

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Giant cell tumor of bone (GCTB) is benign tumor that can cause significant osteolysis and bone destruction at the epiphysis of long bones. Osteoclasts are thought to be highly associated with osteolysis in GCTB. However, the migration of osteoclasts in GCTB remains unclear. A deeper understanding of the complex tumor microenvironment is required in order to delineate the migration of osteoclasts in GCTB. In this study, samples were isolated from one patient diagnosed with GCTB. Single-cell RNA sequencing (scRNA-seq) was used to detect the heterogeneity of GCTB. Multiplex immunofluorescence staining was used to evaluate the cell subtypes identified by scRNA-seq. A total of 8,033 cells were obtained from one patient diagnosed with GCTB, which were divided into eight major cell types as depicted by a single-cell transcriptional map. The osteoclasts were divided into three subsets, and their differentiation trajectory and migration status were further analyzed. Osteoclast migration may be regulated via a series of genes associated with cell migration. Furthermore, four signaling pathways (RANKL, PARs, CD137 and SMEA3 signaling pathway) were found to be highly associated with osteoclast migration. This comprehensive single-cell transcriptome analysis of GCTB identified a series of genes associated with cell migration as well as four major signaling pathways that were highly related to the migration of osteoclasts in GCTB. Our findings broaden the understanding of GCTB bionetworks and provides a theoretical basis for anti-osteolysis therapy against GCTB in the future.

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“…Distinct H3F3A and H3F3B driver mutations de ne chondroblastoma and giant cell tumor of bone (50). Absence of H3F3A mutation in a subset of malignant giant cell tumor of bone (51). H3F3A promotes lung cancer cell migration through intronic regulation (52).…”

Section: Discussionmentioning

confidence: 99%

MiR-26a-1 Promotes DNA Damage Repair by Inhibiting Sirt1 and KDM5A in Human Liver Cancer Stem Cells

Wang¹,

Li²,

Qin³

et al. 2021

Preprint

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Background: Although miR-26a-1 was down-regulated expressin in several cancers, the role of miR-26a-1in malignancies has yet to be systematically elucidated. Methods: RT-PCR, Western blotting and tumorigenesis test in vitro and in vivo were performed to analyze the signaling pathway. Results: miR-26a-1 inhibits the NAD(+)-dependent deacetylase Sirt1 expression by targeting the 3' non-coding region of Sirt1 which enhances the acetylation modification of H4 on the 16th lysine of histone and the expression of protein arginine methyltransferase PRMT6. Therefore, miR-26a-1 promotes arginine methylation modification of POLB (R137) and histone. On the other hand, miR-26a-1 inhibits the expression of KDM5A by targeting its 3' non-coding region, which enhances the methylation modification of histone H3 ysine 4. Moreover, miR-26a-1 enhances the expression of histone methyltransferase SETD2 dependent on H3K4me3 and further increases the trimethylation modification of the histone H3 lysine 36 . Significantly, miR-26a-1 promotes the formation of DNA damage repair complex (Rad51-PARP1-ATR-ATM-hMSH6-XRCC-POLB-SKP2) via H3K36me3. In particular, it was found that miR-26a-1 inhibited the function of long non-coding RNA HULC and promoted the formation of DNA damage repair complex. Furthermore, miR-26a-1 promotes the DNA damage repair ability by promoting the DNA damage repair complex to bind to the DNA damage site, thereby inhibiting the DNA damage of liver cancer stem cells. In particular, miR-26a-1 enhanced the binding of H3F3A to Skp2, CUL1, and F-box at the DNA damage site and enhanced the protein ubiquitination modification of H3F3A, which promoted Histone H3 replaces H3F3A by degrading H3F3A, realizing the renewal of histones after DNA damage repair. It was further found that miR-26a-1 inhibited the formation and instability of DNA microsatellites by promoting DNA damage repair, thereby affecting the expression of several cyclins and protein kinases in liver cancer stem cells, such as, inhibiting CDK2 and CyclinE , CDK4, CyclinD1, CDK6, CDK8, CyclinM2, CDK15, pRB, PCNA, MAP3K2, PGK1 and promoting RB, P18, P21/WAF1/Cip1, and thus inhibited the growth of liver cancer stem cells. Strikingly, the rescued-test further confirmed that excessive Sirt1 and KDM5A abrogated the oncogenic function of miR-26a-1. Conclusions: miR26a-1 may acts as the potential biomarker and therapeutic target for liver cancer.

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Absence of H3F3A mutation in a subset of malignant giant cell tumor of bone

Cited by 40 publications

References 30 publications

Late Local Recurrence of Bone Giant Cell Tumors Associated with an Increased Risk for Malignant Transformation

Late Local Recurrence of Bone Giant Cell Tumors Associated with an Increased Risk for Malignant Transformation

Single-Cell RNA Sequencing Reveals the Migration of Osteoclasts in Giant Cell Tumor of Bone

MiR-26a-1 Promotes DNA Damage Repair by Inhibiting Sirt1 and KDM5A in Human Liver Cancer Stem Cells

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