Constitutional 3p26.3 terminal microdeletion in an adolescent with neuroblastoma

Pezzolo, Annalisa; Sementa, Angela Rita; Lerone, Margherita; Morini, Martina; Ognibene, Marzia; Defferrari, Raffaella; Mazzocco, Katia; Conte, Massimo; Gigliotti, Anna Rita; Garaventa, Alberto; Pistoia, Vito; Varesio, Luigi

doi:10.1080/15384047.2017.1312231

Cited by 12 publications

(19 citation statements)

References 26 publications

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“…Lastowska et al found an overall downregulation of CHL1 in 28 tumor samples that did not impact on the individual prognosis [20]. Conversely, low CHL1 gene expression in 417 neuroblastoma samples was significantly correlated to a reduced overall survival [21]. That parallels our findings of positive protein expression of CHL1 in low tumor grades Hughes 1a/b by immunohistochemistry only.…”

Section: Discussionsupporting

confidence: 88%

CHL1 and NrCAM are primarily expressed in low grade pediatric neuroblastoma

et al. 2019

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AbstractBackgroundNeural cell adhesion molecules like close homolog of L1 protein (CHL1) and neuronal glia related cell adhesion molecule (NrCAM) play an important role in development and regeneration of the central nervous system. However, they are also associated with cancerogenesis and progression in adult malignancies, thus gain increasing importance in cancer research. We therefore studied the expression of CHL1 and NrCAM according to the course of disease in children with neuroblastoma.MethodsCHL1 and NrCAM expression levels were histologically assessed by tissue microarrays from surgically resected neuroblastoma specimens of 56 children. Expression of both markers was correlated to demographics as well as clinical data including metastatic dissemination and survival.ResultsCHL1 was expressed in 9% and NrCAM in 51% of neuroblastoma tissue samples. Expression of CHL1 was higher in patients with low Hughes grade 1a/b (p=0.01). NrCAM was more often detected in patients with a low International Staging System (INSS) score 1/2 (p=0.04).ConclusionCHL1 and NrCAM expression was associated with low-grade pediatric neuroblastoma. These adhesion molecules may play a role in early tumor development of neuroblastoma.

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Section: Discussionsupporting

confidence: 88%

CHL1 and NrCAM are primarily expressed in low grade pediatric neuroblastoma

et al. 2019

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“…Each hybridization produced a pair of 16‐bit images, which were processed using the Agilent Feature Extraction 10.5 Software. The data were analyzed using the Genomic Workbench 7.0.40 software (Agilent), the altered chromosomal regions and breakpoints events were detected using ADM‐1 (threshold 10) with 0.5 Mb window size to reduce false positives . Amplifications were defined as loci with log 2 ratio ≥ 2 and loci with log 2 ratio ≥ 3.5 were considered as high level of amplifications.…”

Section: Methodsmentioning

confidence: 99%

Genomic coamplification of CDK4/MDM2/FRS2 is associated with very poor prognosis and atypical clinical features in neuroblastoma patients

Amoroso

Ognibene

Morini

et al. 2019

Genes Chromosomes & Cancer

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Neuroblastoma (NB) is the most common extracranial malignant tumor of childhood and is characterized by a broad heterogeneity in clinical presentation and evolution. Recent advances in pangenomic analysis of NB have revealed different recurrent chromosomal aberrations. Indeed, it is now well established that the overall genomic profile is important for treatment stratification. In previous studies, 11 genes were shown to be recurrently amplified (ODC1, ALK, GREB1, NTSR2, LIN28B, MDM2, CDK4, MYEOV, CCND1, TERT, and MYC) besides MYCN, with poor survival of NB patients harboring these amplifications being suggested. Genomic profiles of 628 NB samples analyzed by array‐comparative genome hybridization (a‐CGH) were re‐examined to identify gene amplifications other them MYCN amplification. Clinical data were retrospectively collected. We additionally evaluated the association of FRS2 gene expression with NB patient outcome using the public R2 Platform. We found eight NB samples with high grade amplification of one or two loci on chromosome arm 12q. The regional amplifications were located on bands 12q13.3‐q14.1 and 12q15‐q21.1 involving the genes CDK4, MDM2, and the potential oncogenic gene FRS2. The CDK4, MDM2, and FRS2 loci were coamplified in 8/8 samples. The 12q amplifications were associated with very poor prognosis and atypical clinical features of NB patients. Further functional and clinical investigations are needed to confirm or refute these associations.

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“…The frequency of NCA revealed that individual chromosomes differed in their likelihood to be lost or gained. In particular, gain appeared to be more frequent in chromosomes 1, 2, 5, 6, 7, 12, 13, 17, 18, and 20; loss was prevalent in chromosomes 3,4,9,10,11,14,16,19,21,22, X, and Y; a similar proportion of losses and gains were observed for chromosomes 8 and 15. To notice, chromosomes 2, 7, 12, 13, and 17 were significantly more frequently gained than any of the other chromosomes and were also lost at a very low frequency.…”

Section: Genomic Profile Analysismentioning

confidence: 84%

“…The Agilent platform is an oligonucleotide‐based microarray with an average resolution of about 25 kb to detect copy‐number variations, and loss of heterozygosity (LOH) of 4 Mb. Raw data were analyzed using the Genomic Workbench 7.0.40 software (Agilent), the altered chromosomal regions and breakpoints, and LOH events were detected using ADM‐1 (threshold 10) with 0.5 Mb window size to reduce false positives . For aberration detection, we have applied the diploid peak centralization algorithm and the legacy centralization algorithm to set the most common ploidy to zero; it was done without assigning ploidy data.…”

Section: Methodsmentioning

confidence: 99%

“…Raw data were analyzed using the Genomic Workbench 7.0.40 software (Agilent), the altered chromosomal regions and breakpoints, and LOH events were detected using ADM-1 (threshold 10) with 0.5 Mb window size to reduce false positives. 16 For aberration detection, we have applied the diploid peak centralization algorithm and the legacy centralization algorithm to set the most common ploidy to zero; it was done without assigning ploidy data. This is needed to ensure that the zero point reflects the most common ploidy state.…”

Section: Genomic Profile Determinationmentioning

confidence: 99%

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Loss of whole chromosome X predicts prognosis of neuroblastoma patients with numerical genomic profile

Parodi

Pistorio

Erminio

et al. 2019

Pediatric Blood & Cancer

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Background Neuroblastoma (NB), a pediatric tumor of the sympathetic nervous system, is characterized by very frequent chromosomal aberrations at the onset of the disease. Identification of further risk factors for relapse, which could lead to increased survival and potentially reduced late effects among survivors, is still urgently needed. Segmental chromosome aberrations (SCA) are associated with poor prognosis, whereas numerical whole‐chromosome aberrations (NCA) are found in patients with a good prognosis; however, a small percentage of the latter patients (10%–15%) subsequently relapse and/or die of disease. Procedure DNA copy‐number data from 174 NB patients with an NCA genomic profile were analyzed. Association between NCA and event‐free survival (EFS) was investigated by the Kaplan–Meier estimator and prognostic decision tree (DT). Results DT identified 65 patients with normal chromosome X and an excellent five‐year EFS (100%) independently from the stage at diagnosis. The association between poor EFS and whole chromosome X alterations was confirmed after stratification into two groups of different expected prognosis and by internal validation via bootstrap analysis. Furthermore, the association was also observed in an independent cohort of NB patients extracted from the data set of the National Cancer Institute TARGET Project for Neuroblastoma, but sample size was small (n = 75) and statistical significance was not achieved. Conclusions Loss of whole chromosome X may represent a new prognostic marker for NB patients with an NCA genomic profile. If confirmed by further studies, this finding could indicate that such patients should be reclassified as intermediate risk and treated accordingly.

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Constitutional 3p26.3 terminal microdeletion in an adolescent with neuroblastoma

Cited by 12 publications

References 26 publications

CHL1 and NrCAM are primarily expressed in low grade pediatric neuroblastoma

CHL1 and NrCAM are primarily expressed in low grade pediatric neuroblastoma

Genomic coamplification of CDK4/MDM2/FRS2 is associated with very poor prognosis and atypical clinical features in neuroblastoma patients

Loss of whole chromosome X predicts prognosis of neuroblastoma patients with numerical genomic profile

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