Abstract
BackgroundRecurrent non-random genomic alterations are the hallmarks of cancer and the characterization of these imbalances is critical to our understanding of tumorigenesis and cancer progression.ResultsWe performed array-comparative genomic hybridization (A-CGH) on cDNA microarrays containing 42,000 elements in neuroblastoma (NB). We found that only two chromosomes (2p and 12q) had gene amplifications and all were in the MYCN amplified samples. There were 6 independent non-contiguous amplicons (10.4–69.4 Mb) on chromosome 2, and the largest contiguous region was 1.7 Mb bounded by NAG and an EST (clone: 757451); the smallest region was 27 Kb including an EST (clone: 241343), NCYM, and MYCN. Using a probabilistic approach to identify single copy number changes, we systemically investigated the genomic alterations occurring in Stage 1 and Stage 4 NBs with and without MYCN amplification (stage 1-, 4-, and 4+). We have not found genomic alterations universally present in all (100%) three subgroups of NBs. However we identified both common and unique patterns of genomic imbalance in NB including gain of 7q32, 17q21, 17q23-24 and loss of 3p21 were common to all three categories. Finally we confirm that the most frequent specific changes in Stage 4+ tumors were the loss of 1p36 with gain of 2p24-25 and they had fewer genomic alterations compared to either stage 1 or 4-, indicating that for this subgroup of poor risk NB requires a smaller number of genomic changes are required to develop the malignant phenotype.ConclusionscDNA A-CGH analysis is an efficient method for the detection and characterization of amplicons. Furthermore we were able to detect single copy number changes using our probabilistic approach and identified genomic alterations specific to stage and MYCN amplification.
Highlights
Recurrent non-random genomic alterations are the hallmarks of cancer and the characterization of these imbalances is critical to our understanding of tumorigenesis and cancer progression
We found that the slope of the fitting line was 0.35, and an observed ratio of 2 by array-comparative genomic hybridization (A-CGH) corresponds to
In this study we explored the genomic alterations in NB from the data generated by A-CGH on a cDNA microarray platform
Summary
Recurrent non-random genomic alterations are the hallmarks of cancer and the characterization of these imbalances is critical to our understanding of tumorigenesis and cancer progression. Genomic alterations in NB have been investigated by cytogenetic, and molecular methods including spectral karyotyping and metaphase comparative genomic hybridization (M-CGH) [2,3,4,5,6]. Based on these studies several genomic alterations have been reported to correlate with prognosis including amplification of the MYCN oncogene (found in 30% of NB) [1,7], gains of 17q (>50%) and loss of 1p36 (30–35%) [1,8,9]. Other recurrent changes including losses of 3p, 4p, 9p, 11q, and 14q, as well as frequent gain of chromosome 7 have been suggested to have relevance to the development and progression of these tumors [9]
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