Genetics of neuroblastoma


Session type:

Peter Ambros

Children's Cancer Research Institute, Vienna, Austria


Modern treatment strategies adjust the therapy of cancer patients according to the predicted biologic behaviour of the individual tumour. This is especially important for neuroblastoma patients, as a subset of neuroblastic tumours will undergo spontaneous regression (in infants and young children) or maturation (in children), whereas others will rapidly progress despite intensive multi-modality therapy. This clinical heterogeneity has been known for decades, but reliable markers for therapy guidance lacked.

The amplification of the MYCN proto-oncogene became the first hallmark of unfavourable tumour behaviour and is used as stratifying element in clinical studies. However, as only a minority of aggressive tumours show this aberration the search for stratifying genomic changes is still ongoing. A number of different segmental aberrations (gains or losses of parts of chromosomes) were found in aggressive tumours indicating their association with aggressive tumour behaviour. Unfortunately, only few data exist on the genomic profile of benign tumours. Thus, it is not clear whether spontaneous regression/maturation may act also in cases with segmental aberrations.

As large patient cohorts need to be studied to come to conclusive results an international effort was undertaken to collect the biological/genetic features of a large cohort of patients. The current INRG (International Neuroblastoma Risk Group) Classification Schema is based on the analysis of 8,800 patient samples and allows directing the therapeutic strategies more adequately varying from watch-and-wait approaches to intensive chemotherapeutic regimes. Besides age and histological features, MYCN status, tumour cell DNA content (ploidy), and, 11q status are included as genetic strata (Cohn, Pearson et al. 2009). With this stratification schema a more precise adjustment of treatment options will be possible. However, still a grey zone exists as not every tumour can be categorized exactly. Thus, large studies validating the impact of genomic and expression differences among tumours with different clinical behaviour are needed.