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. 2012 Oct 9;107(8):1418-22.
doi: 10.1038/bjc.2012.375. Epub 2012 Sep 13.

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

G Schleiermacher  1 , V Mosseri, W B London, J M Maris, G M Brodeur, E Attiyeh, M Haber, J Khan, A Nakagawara, F Speleman, R Noguera, G P Tonini, M Fischer, I Ambros, T Monclair, K K Matthay, P Ambros, S L Cohn, A D J Pearson
Affiliations

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

G Schleiermacher et al. Br J Cancer. .

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.

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Figures

Figure 1
Figure 1
Frequency of detection the genetic alterations chromsome 1p deletion, chromosome 11q deletion and chromosome 17q gain among 397 patients without MYCN amplification harbouring at least one genetic alteration in the INRG database.
Figure 2
Figure 2
Event-free and overall survival in 505 patients without MYCN amplification for whom a genomic type could be attributed. ‘Segmental’ genomic type: presence of either chromosome 1p deletion and/or chromosome 11q deletion and/or chromosome 17q gain. No segmental changes: no alteration for all three genetic markers.
See this image and copyright information in PMC

References

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