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

Abstract

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.

Role of GOLPH3 and TPX2 in Neuroblastoma DNA Damage Response and Cell Resistance to Chemotherapy

“…We analyzed by array-CGH the genome wide copy number variations in the DNA extracted from the 10 NB samples here considered coming from pre-chemotherapy surgical resection using Human Genome CGH Microarray 4X 180K Kit (Agilent Technologies, Santa Clara, CA, USA), with a mean resolution of approximately 25 kb, as previously described [93]. Tumor DNAs were extracted using the QIAamp DNA Extraction Kit (Qiagen, Hilden, Germany), according to the manufacturer’s instructions.…”

“…Images of the array were acquired with the Agilent C Scanner (Agilent Technologies), 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 the algorithm ADM-1 (threshold 10) with 0.5 Mb window size to reduce false positives [93]. The raw data are stored in the BIT-NB Bio Bank of IRCCS Gaslini.…”

Chromosome 10 abnormality predicts prognosis of neuroblastoma patients with bone marrow metastasis

“…NB in stages I, II, and 4S is mostly triploid, with relatively good prognosis. Patients often have chromosome 6, 7, and 17 gains and chromosomes 3, 4, 11, and 14 losses [ 17 ]. Parodi et al came to a preliminary conclusion that the prognosis of children with NB and whole X-chromosome-loss is relatively poor, which can be used as a new prognostic indicator, and patients with this chromosomal abnormality should be treated in the IR group [ 18 ].…”

Chromosome 10 Abnormality Predicts Prognosis of Neuroblastoma Patients With Bone Marrow Metastasischromosome 10 Abnormality Predicts Prognosis of Neuroblastoma Patients With Bone Marrow Metastasis

“…They often have typical chromosomes 6, 7 and 17 gains and chromosomes 3, 4, 11 and 14 losses [15]. Parodi et al came to a preliminary conclusion that the prognosis of the whole X-chromosome-loss NB children is relatively poor, which can be used as a new prognostic indicator, and this kind of children should be treated in the IR group [16]. Marked by centromere, each chromosome is divided into long arm (q) and short arm (p).…”