TH and DCX mRNAs in peripheral blood and bone marrow predict outcome in metastatic neuroblastoma patients

Yáñez, Yania; Hervás, David; Grau, Elena; Oltra, Silvestre; Pérez, G.; Palanca, Sarai; Bermúdez, Mar; Márquez-Vega, Catalina; Cañete, Adela; Castel, Victoria

doi:10.1007/s00432-015-2054-7

Cited by 36 publications

(31 citation statements)

References 25 publications

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“…Importantly, to provide sufficient follow-up data, the analy- Many studies have explored potential methods of identifying HR-NBL patients with particularly poor outcomes. These include quantification of tumour-related mRNA in blood or BM samples, 10,26,27 semi-quantitative scoring of mIBG response, 8,9,28 identification of specific tumour genetic aberrations such as ALK mutation or TERT rearrangements [29][30][31] and multiple different gene expression classifiers. [32][33][34] As yet, these techniques have not yet been simultaneously evaluated in sufficiently large homogeneously treated HR-NBL patient populations.…”

Section: Discussionmentioning

confidence: 99%

Risk stratification of high‐risk metastatic neuroblastoma: A report from the HR‐NBL‐1/SIOPEN study

Morgenstern

Pötschger

Moreno

et al. 2018

Pediatric Blood & Cancer

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Section: Discussionmentioning

confidence: 99%

Risk stratification of high‐risk metastatic neuroblastoma: A report from the HR‐NBL‐1/SIOPEN study

Morgenstern

Pötschger

Moreno

et al. 2018

Pediatric Blood & Cancer

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“…Yanez et al reported high levels of DCX mRNA detection by RT-qPCR in the PB and BM at diagnosis. According to them, high levels of DCX in BM independently predicted poor event-free survival and overall survival in NB patients (Yanez et al, 2016). They consequently suggested that DCX mRNA levels in PB and BM assessed by RT-qPCR may be considered in new pretreatment risk stratification strategies to reliably estimate outcome differences in metastatic NB patients.…”

Section: Dynamic Involvement Of DCX In Cancersmentioning

confidence: 99%

Distinct Features of Doublecortin as a Marker of Neuronal Migration and Its Implications in Cancer Cell Mobility

Ayanlaja

Xiong

Gao

et al. 2017

Front. Mol. Neurosci.

107

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Neuronal migration is a critical process in the development of the nervous system. Defects in the migration of the neurons are associated with diseases like lissencephaly, subcortical band heterotopia (SBH), and pachygyria. Doublecortin (DCX) is an essential factor in neurogenesis and mutations in this protein impairs neuronal migration leading to several pathological conditions. Although, DCX is capable of modulating and stabilizing microtubules (MTs) to ensure effective migration, the mechanisms involved in executing these functions remain poorly understood. Meanwhile, there are existing gaps regarding the processes that underlie tumor initiation and progression into cancer as well as the ability to migrate and invade normal cells. Several studies suggest that DCX is involved in cancer metastasis. Unstable interactions between DCX and MTs destabilizes cytoskeletal organization leading to disorganized movements of cells, a process which may be implicated in the uncontrolled migration of cancer cells. However, the underlying mechanism is complex and require further clarification. Therefore, exploring the importance and features known up to date about this molecule will broaden our understanding and shed light on potential therapeutic approaches for the associated neurological diseases. This review summarizes current knowledge about DCX, its features, functions, and relationships with other proteins. We also present an overview of its role in cancer cells and highlight the importance of studying its gene mutations.

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“…Freezing testicular tissue allows subsequent transplantation either by infusion of a testicular cell suspension into the seminiferous tubules (26) or intra-testicular grafting of tissue (27). However, >60% of children with metastatic NB have circulating tumor cells at the time of diagnosis (28). Although testis is not the most frequent NB invasion site, numerous cases of testicular NB metastasis have been described previously.…”

Section: Discussionmentioning

confidence: 99%

RT-qPCR for PHOX2B mRNA is a highly specific and sensitive method to assess neuroblastoma minimal residual disease in testicular tissue

et al. 2017

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Neuroblastoma (NB) is the most common type of extracranial solid tumor in children with a high prevalence in toddlers. For childhood cancer survivors, preservation of reproductive potential is an important factor for quality of life. The optimization of NB minimal residual disease (MRD) detection in testicular tissue is crucial to evaluate the risk of malignant cell reintroduction. The first step in the present study was to assess the accuracy of reverse transcription-quantitative polymerase chain reaction (RT-qPCR) to detect tyrosine hydroxylase (TH), paired-like homeobox 2b (PHOX2B) and doublecortin (DCX) mRNA expression in frozen/thawed testicular tissues of patients with non-obstructive azoospermia (NOA) contaminated (in vitro model) with an increasing number of IMR-32 and SK-N-SH NB cells. Testicular tissues were frozen by slow or snap freezing. The second step was to determine the expression levels of these markers in testicular samples from 4 pre-pubertal males (2 with stage IV NB and 2 with non-NB malignancy). The yield of extracted RNA was similar in testicular samples frozen by slow or snap freezing. In the in vitro model, TH and DCX transcripts were detected in uncontaminated testicular tissues, whereas PHOX2B mRNA was not detected. There was a strong positive association between the number of NB cells used for contamination and PHOX2B transcript levels. For IMR-32 and SK-N-SH NB cell lines, specificity and sensitivity rates of detection were 100% for PHOX2B following in vitro contamination with 10 tumor cells. In testicular samples from pre-pubertal males with and without NB, PHOX2B mRNA expression was not observed, but high expression levels of TH and DCX mRNA were detected, which were similar to expression detected in the in vitro model. Among the markers used in blood and bone marrow for NB MRD studies, the detection of PHOX2B transcripts by RT-qPCR may provide an accurate assessment of NB cells in testicular tissues from males who require fertility preservation.

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TH and DCX mRNAs in peripheral blood and bone marrow predict outcome in metastatic neuroblastoma patients

Cited by 36 publications

References 25 publications

Risk stratification of high‐risk metastatic neuroblastoma: A report from the HR‐NBL‐1/SIOPEN study

Risk stratification of high‐risk metastatic neuroblastoma: A report from the HR‐NBL‐1/SIOPEN study

Distinct Features of Doublecortin as a Marker of Neuronal Migration and Its Implications in Cancer Cell Mobility

RT-qPCR for PHOX2B mRNA is a highly specific and sensitive method to assess neuroblastoma minimal residual disease in testicular tissue

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