Segmental chromosomal alterations have prognostic impact in neuroblastoma: a report from the INRG project

Abstract

Background:In the INRG dataset, the hypothesis that any segmental chromosomal alteration might be of prognostic impact in neuroblastoma without MYCN amplification (MNA) was tested.Methods:The presence of any segmental chromosomal alteration (chromosome 1p deletion, 11q deletion and/or chromosome 17q gain) defined a segmental genomic profile. Only tumours with a confirmed unaltered status for all three chromosome arms were considered as having no segmental chromosomal alterations.Results:Among the 8800 patients in the INRG database, a genomic type could be attributed for 505 patients without MNA: 397 cases had a segmental genomic type, whereas 108 cases had an absence of any segmental alteration. A segmental genomic type was more frequent in patients >18 months and in stage 4 disease (P<0.0001). In univariate analysis, 11q deletion, 17q gain and a segmental genomic type were associated with a poorer event-free survival (EFS) (P<0.0001, P=0.0002 and P<0.0001, respectively). In multivariate analysis modelling EFS, the parameters age, stage and a segmental genomic type were retained in the model, whereas the individual genetic markers were not (P<0.0001 and RR=2.56; P=0.0002 and RR=1.8; P=0.01 and RR=1.7, respectively).Conclusion:A segmental genomic profile, rather than the single genetic markers, adds prognostic information to the clinical markers age and stage in neuroblastoma patients without MNA, underlining the importance of pangenomic studies.

Clinical, Biologic, and Prognostic Differences on the Basis of Primary Tumor Site in Neuroblastoma: A Report From the International Neuroblastoma Risk Group Project

“…We evaluated each of these variables separately and also created a pooled variable reflecting the presence of segmental chromosomal aberration if at least one of these aberrations was present. 13 Clinical and biologic features were compared between groups defined by primary tumor site using 2 tests (for categorical variables) or t test or analysis of variance between groups (for continuous variables). We fit logistic regression models to describe the odds of having MYCN amplification according to primary tumor site after controlling for key potential confounders.…”

Alternative NHEJ Pathway Components Are Therapeutic Targets in High-Risk Neuroblastoma

“…11,12). This implies that segmental alterations could represent either an intact NHEJ mechanism processing abnormally high numbers of DSB or an underlying abnormality of DNA repair and maintenance (13).…”

Characterization of Chromosomal Aberrations in Neuroblastoma Formalin-Fixed Paraffin- Embedded Specimens with Standard ArrayCGH Procedure - Preliminary Experience

“…This abnormality is associated with poor prognosis, and is frequently coexisted with other biomarkers of aggressive disease such as MYCN amplification, older age, and chromosome 1p36 deletion. Loss of 1p36 region occurs in approximately a quarter of NB tumors and also predicted adverse outcome [2,3,7,11,13]. In addition, a recent INRG report on non-MYCN amplified tumors determined that it is not single genetic markers, but the overall segmental genomic profile of tumors that adds information to patient prognosis [11].…”

“…Aggressive metastatic tumors are characterized by a high number of SCAs and a low number of Numerical Changes (NCAs). On the whole, genome-wide studies have demonstrated that critical chromosomal damages occur more frequently in older patients and that SCAs accumulate in an age-dependent manner, as supported by Schleiermacher and Coco [8][9][10][11][12].…”