Exome sequence analysis of Kaposiform hemangioendothelioma: identification of putative driver mutations

Egashira, Sho; Jinnin, Masatoshi; Harada, Masaki; Masuguchi, Shinichi; Fukushima, Satoshi; Ihn, Hironobu

doi:10.1590/abd1806-4841.20165026

Cited by 5 publications

(4 citation statements)

References 13 publications

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“…Evidence from basic research proposing that HHV8 is an integrating oncovirus that causes amplification and activation of oncogenes needs to be further investigated by the sequencing of early and advanced lesions considering the latent state in which HHV8 has been reported to exist [ 52 ] as the clonality of HHV8 integration is sometimes questioned. While many studies have been published reporting genetic alterations in KS samples, few have analysed whether these are driver mutations that might be involved in oncogenesis [ 53 , 54 ].…”

Section: Discussionmentioning

confidence: 99%

Clonality, Mutation and Kaposi Sarcoma: A Systematic Review

Ruiz

Armon

Watanabe

et al. 2022

Cancers

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Background: It remains uncertain whether Kaposi sarcoma (KS) is a true neoplasm, in that it regresses after removal of the stimulus to growth (as HHV8) when immunosuppression is reduced. We aimed to summarize the available evidence on somatic mutations and clonality within KS to assess whether KS is a neoplasm or not. Methods: Medline and Web of Science were searched until September 2020 for articles on clonality or mutation in KS. Search strings were supervised by expert librarians, and two researchers independently performed study selection and data extraction. An adapted version of the QUADAS2 tool was used for methodological quality appraisal. Results: Of 3077 identified records, 20 publications reported on relevant outcomes and were eligible for qualitative synthesis. Five studies reported on clonality, 10 studies reported on various mutations, and 5 studies reported on chromosomal aberrations in KS. All studies were descriptive and were judged to have a high risk of bias. There was considerable heterogeneity of results with respect to clonality, mutation and cytogenetic abnormalities as well as in terms of types of lesions and patient characteristics. Conclusions: While KS certainly produces tumours, the knowledge is currently insufficient to determine whether KS is a clonal neoplasm (sarcoma), or simply an aggressive reactive virus-driven lesion.

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Section: Discussionmentioning

confidence: 99%

Clonality, Mutation and Kaposi Sarcoma: A Systematic Review

Ruiz

Armon

Watanabe

et al. 2022

Cancers

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“…Additionally, only a few studies have focused on the initiation and progression of KHE at the genetic level. Egashira et al (42) performed exome sequencing using DNA from a patient with KHE and identified germline missense single nucleotide variants in the tumour protein p53 and adenomatous polyposis coli genes, and tumour-specific somatic mutations in the integrin subunit β2, interleukin 32 and death inducer-obliterator 1 genes. To provide effective experimental evidence for genetic diagnosis and therapy in patients with KHE/KMP, additional in vivo and in vitro studies are warranted.…”

Section: Discussionmentioning

confidence: 99%

Local suture ligation‑assisted percutaneous sclerotherapy for Kasabach‑Merritt phenomenon‑associated kaposiform haemangioendothelioma

Wen

et al. 2018

Oncol Lett

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Kaposiform haemangioendotheliomas (KHEs) complicated by the Kasabach-Merritt phenomenon (KMP) are rare and severe neoplastic lesions often associated with locally aggressive disease, consumption coagulopathy and high mortality rates. Current regimens have yet to achieve a satisfactory therapeutic effect. Thus, an effective and minimally invasive approach for treating complex KHE/KMP cases is necessary for clinical management. The present case series describes patients with KHE/KMP who underwent local suture ligation-assisted percutaneous sclerotherapy to minimise surgical trauma and ensure effective treatment. Between September 2015 and September 2017, 3 consecutive patients with KHE/KMP underwent staged local suture ligation-assisted percutaneous sclerotherapy. Of these patients, 2 presented with medical histories of corticosteroid treatment with unsatisfactory outcomes. The patients underwent a stepwise synthetic serial therapy programme consisting of percutaneous sclerotherapy and adjunctive pharmacotherapy accompanied by a suture ligation procedure. Clinical, radiological, pathological and laboratory data were analysed to evaluate the outcomes of the therapy. All patients were successfully managed with the proposed procedure. Significant relief of clinical symptoms and improvements in haematological indicators were achieved. No recurrence or complications were observed during regular follow-up (4, 19 and 28 months). In conclusion, local suture ligation-assisted percutaneous sclerotherapy was demonstrated to be a safe and effective treatment for KHE/KMP, being minimally invasive, involving simple manipulation and providing a clear treatment benefit in certain cases. Further studies involving larger sample sizes are required to thoroughly evaluate the procedure, which can potentially be used as a novel therapeutic option for KHE/KMP treatment.

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“…An N-terminal truncation of Dido1 (Dido1ΔNT), results in genomic instability, due to centrosome amplification and centromere localized DNA breaks (20,21), leading to myeloid malignancies (2). In the last years, several independent studies linked genetic alterations in Dido1 to different cancer types: Melanoma (22), Kaposiform hemangioendothelioma (23), Chronic Myeloid Leukemia (24), Prostate cancer (25), Head and neck cancer (26), Hepatic neuroendocrine tumours (27), Colorectal cancer (28), Bladder cancer (29), Renal cell carcinoma (30), and Esophageal cancer (31,32). Some of these studies suggested an important role of epigenetic modifications and chromatin remodelling processes in cancer development.…”

Section: Introductionmentioning

confidence: 99%

DIDO3 acts at the interface of RNAPII transcription and chromatin structure regulation

Pons

Serra

Pazos

et al. 2021

Preprint

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Chromatin structure and organization has a key role in gene expression regulation. Here, we integrated ChIP-seq, RNA-seq, Hi-C, epigenetic, and cancer-related mutations data to get insight into the role of Death Inducer Obliterator gene (Dido1) in RNA pol II (RNAPII) transcription and chromatin structure regulation. Analysis of ChIP-seq data of DIDO3, the largest protein isoform of Dido1, revealed binding-sites overlap about 70% with RNAPII and H3K36me3 in the mouse genome, but also significant overlap 10-30% with Polycomb, CTCF, H3K4me3, and H3K27ac. Based on this analysis we propose that DIDO3 PHD domain interacts with H3K36me3 posttranslational modification. Integrating multi-omics data we describe how DIDO3 potentially recruit several transcription factors, including RNAPII, and also regulates genes transcribing those same transcription factors. DIDO3 regulation of the genes traduced into proteins to which it binds puts DIDO3 in the center of intricate feedback loops. We showed, by using data from a DIDO3 mutant, that DIDO3 C-terminus is responsible for most of these transcriptional regulation, and is also implicated in other very important pathways by regulating genes encoding for Polycomb-accessory proteins, subunits of the SWI/SNF chromatin remodelling, or Set1/COMPASS chromatin modifier complexes. These multi-protein complexes control gene activation or silencing and also play a role in tumour development. DIDO3 C-terminus region and splice-site for alternative DIDO2/DIDO3 protein isoforms tended to accumulate recurrent truncating mutations identified in the TCGA Pan-Cancer dataset. We hypothesize that deregulation of DIDO3, as it happens with large epigenetic complexes and long-range interactions, leads to cell differentiation deficiency and cancer development. Overall, we propose here a molecular mechanism by which DIDO3, favour RNAPII pausing and long-range chromatin interactions.

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Exome sequence analysis of Kaposiform hemangioendothelioma: identification of putative driver mutations

Cited by 5 publications

References 13 publications

Clonality, Mutation and Kaposi Sarcoma: A Systematic Review

Clonality, Mutation and Kaposi Sarcoma: A Systematic Review

Local suture ligation‑assisted percutaneous sclerotherapy for Kasabach‑Merritt phenomenon‑associated kaposiform haemangioendothelioma

DIDO3 acts at the interface of RNAPII transcription and chromatin structure regulation

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