Metastatic neuroblastoma in a patient with ROHHAD: A new alert regarding the risk of aggressive malignancies in this rare condition

Calvo, Charlotte; Storey, Caroline; Morcrette, Guillaume; Akl, Pia; Fréneaux, Paul; Pierron, Gaëlle; Trang, Ha; Aerts, Isabelle; Schleiermacher, Gudrun; Philippe‐Chomette, Pascale; Carel, Jean‐Claude; Bourdeaut, Franck

doi:10.1002/pbc.27906

Cited by 8 publications

(6 citation statements)

References 10 publications

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“…Although numerous treatments for NB currently exist, patients with NB have only 40% survival rate (2,30). A novel treatment is therefore needed to improve survival rate.…”

Section: Discussionmentioning

confidence: 99%

“…Neuroblastoma (NB) is an embryonic tumor derived from sympathetic neural crest cells ( 1 , 2 ). It is the most common type of extracranial solid tumor found in children and the most common type of malignant tumor found in infants and young children, with an incidence rate of 10.5 per million children younger than 14 years old ( 3 – 5 ).…”

Section: Introductionmentioning

confidence: 99%

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Determination of long non‑coding RNAs associated with EZH2 in neuroblastoma by RIP‑seq, RNA‑seq and ChIP‑seq

Xie

Zhang

et al. 2020

Oncol Lett

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Neuroblastoma (NB) is the most common type of extracranial solid tumor found in children. Despite several treatment options, patients with advanced stage disease have a poor prognosis. Previous studies have reported that enhancer of zeste homolog 2 (EZH2) and long non-coding RNAs (lncRNAs) have abnormal expression levels in NB and participate in tumorigenesis and NB development. However, the association between EZH2 and lncRNAs remain unclear. In the present study, RNA immunoprecipitation-sequencing (RIP-seq) was used to analyze the lncRNAs binding to EZH2. Following EZH2 knockdown via short hairpin RNA, RNA-seq was performed in shEZH2 and control groups in SH-SY5Y cells. Chromatin IP (ChIP)-seq was used to determine the genes that may be regulated by EZH2. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to identify the signaling pathways involved in NB. The results from RIP-seq identified 94 lncRNAs, including SNHG7, SNHG22, KTN-AS1 and Linc00843. Furthermore, results from RNA-seq demonstrated that, following EZH2 knockdown, 448 genes were up-and 571 genes were downregulated, with 32 lncRNAs up-and 35 downregulated and differentially expressed compared with control groups. Certain lncRNAs, including MALAT1, H19, Linc01021 and SNHG5, were differentially expressed in EZH2-knockdown group compared with the control group. ChIP-seq identified EZH2 located in the promoter region of 138 lncRNAs including CASC16, CASC15, LINC00694 and TBX5-AS1. In summary, the present study demonstrated that certain lncRNAs directly bound EZH2 and regulated EZH2 expression levels. A number of these lncRNAs that are associated with EZH2 may participate in NB tumorigenesis.

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“…Although numerous treatments for NB currently exist, patients with NB have only 40% survival rate (2,30). A novel treatment is therefore needed to improve survival rate.…”

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Determination of long non‑coding RNAs associated with EZH2 in neuroblastoma by RIP‑seq, RNA‑seq and ChIP‑seq

Xie

Zhang

et al. 2020

Oncol Lett

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“…The common locations for these tumors are intraabdominal, specifically adrenal, or paravertebral [ 1 , 3 ]. The majority of these tumors are benign, but a report of malignant neuroblastoma with ROHHAD necessitates screening [ 4 ]. The resection of NET in at least two ROHHAD patients resulted in no symptomatic improvement [ 5 ].…”

Section: Discussionmentioning

confidence: 99%

The Perfect Storm: A Case of Rapid-Onset Obesity With Hypoventilation, Hypothalamic, Autonomic Dysregulation, Neuroendocrine Tumor (ROHHADNET) With Heart Failure, Narcolepsy, and a Rare Location of a Pelvic Neuroendocrine Tumor

Roby,

Smith Beltran,

Finch

et al. 2023

Cureus

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Rapid-onset obesity with hypothalamic dysfunction, hypoventilation, and autonomic dysregulation (ROHHAD) syndrome is a rare disease of concurrent respiratory dysfunction and autonomic dysregulation with endocrine abnormalities. ROHHADNET includes ROHHAD plus coexisting neuroendocrine tumors (NETs). We describe an eight-year-old boy, who originally presented at four years of age with rapid weight gain and hyperhidrosis and who developed mild obstructive sleep apnea (OSA). His clinical course was eventually complicated by hypoxic respiratory failure requiring admission to the pediatric intensive care unit (PICU). Echocardiogram at that time demonstrated dilated cardiomyopathy left ventricular ejection fraction (LVEF) of 28% at time of admission. His respiratory failure persisted despite average volume-assured pressure support (AVAPS) around the clock leading to tracheostomy placement for cardiopulmonary support. He also demonstrated autonomic instability with multiple pituitary hormone deficiencies. Computed tomography (CT) imaging of the abdomen and pelvis demonstrated a presacral soft tissue mass consistent with a tumor of neural crest origin. Daytime somnolence and confusion progressed and a low cerebrospinal fluid hypocretin level revealed a diagnosis of narcolepsy type 1.

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“…Up to now, no therapeutic protocol is available for ROHHAD syndrome, and patient management remains challenging. The underlying aetiology is still unknown and several hypotheses have been formulated, of which the genetic one is among the most accredited and explored so far, also given the clinical proximity to Congenital Central Hypoventilation Syndrome (CCHS) and Prader-Willi syndrome (PWS) ( Patwari et al, 2011 ; Rand et al, 2011 ; Barclay et al, 2015 ; Chow et al, 2015 ; Thanker et al, 2015 ; Barclay et al, 2016 ; Barclay et al, 2018 ; Lee et al, 2018 ; Calvo et al, 2019 ; Giacomozzi et al, 2019 ; Lazea et al, 2021 ; Artamonova et al, 2022 ; Ceccherini et al, 2022 ; Mandel-Brehm et al, 2022 ). However, the genetic etiology of ROHHAD lacks evidence such as intra-family segregation, and also the failure to detect single gene defects allows to exclude a simple mendelian inheritance.…”

Section: Introductionmentioning

confidence: 99%

Whole genome sequencing in ROHHAD trios proved inconclusive: what’s beyond?

Grossi,

Rusmini,

Cusano

et al. 2023

Front. Genet.

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Rapid-onset Obesity with Hypothalamic dysfunction, Hypoventilation and Autonomic Dysregulation (ROHHAD) is a rare, life-threatening, pediatric disorder of unknown etiology, whose diagnosis is made difficult by poor knowledge of clinical manifestation, and lack of any confirmatory tests. Children with ROHHAD usually present with rapid onset weight gain which may be followed, over months or years, by hypothalamic dysfunction, hypoventilation, autonomic dysfunction, including impaired bowel motility, and tumors of neural crest origin. Despite the lack of evidence of inheritance in ROHHAD, several studies have been conducted in recent years that have explored possible genetic origins, with unsuccessful results. In order to broaden the search for possible genetic risk factors, an attempt was made to analyse the non-coding variants in two trios (proband with parents), recruited in the Gaslini Children’s Hospital in Genoa (Italy). Both patients were females, with a typical history of ROHHAD. Gene variants (single nucleotide variants, short insertions/deletions, splice variants or in tandem expansion of homopolymeric tracts) or altered genomic regions (copy number variations or structural variants) shared between the two probands were searched. Currently, we have not found any potentially pathogenic changes, consistent with the ROHHAD clinical phenotype, and involving genes, regions or pathways shared between the two trios. To definitively rule out the genetic etiology, third-generation sequencing technologies (e.g., long-reads sequencing, optical mapping) should be applied, as well as other pathways, including those associated with immunological and autoimmune disorders, should be explored, making use not only of genomics but also of different -omic datasets.

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Metastatic neuroblastoma in a patient with ROHHAD: A new alert regarding the risk of aggressive malignancies in this rare condition

Cited by 8 publications

References 10 publications

Determination of long non‑coding RNAs associated with EZH2 in neuroblastoma by RIP‑seq, RNA‑seq and ChIP‑seq

Determination of long non‑coding RNAs associated with EZH2 in neuroblastoma by RIP‑seq, RNA‑seq and ChIP‑seq

The Perfect Storm: A Case of Rapid-Onset Obesity With Hypoventilation, Hypothalamic, Autonomic Dysregulation, Neuroendocrine Tumor (ROHHADNET) With Heart Failure, Narcolepsy, and a Rare Location of a Pelvic Neuroendocrine Tumor

Whole genome sequencing in ROHHAD trios proved inconclusive: what’s beyond?

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