1. The neuroblastoma genome Studies of genomic alterations using copy number microarray analyzes Tommy Martinsson Department of Clinical Genetics Sahlgrenska University Hospital University of Gothenburg Gothenburg, Sweden NBCNS meeting - Solbacka Sept 19, 2008 tommy.martinsson@gu.se

2. Affymetrix 250k NspI array App. 260.000 SNP positions Average spacing 1 SNP / 12.000 bp Analysis using the CNAG 3.0 software (http://www.genome.umin.jp/) Copy number detection in Neuroblastomas using the Affymetrix Microarray platform

3. Normal ctrl.

4. NBL case 1p deletion MYCN amplification 17q gain

5. 1p deletion in two NBL cases

6. MYCNALK Three NBL cases with MYCN amplification

7. For more information on our NBL arrayCGH data set, see recent publication: Carén et al., BMC Genomics. 2008 9:353.

8. Three NBL cases: NMA + few additional structural changes

9. Three NBL cases: No structural aberrations - only numerical changes

10. A few omitted slides - data will be submitted for publication soon

11. SNP arrays enable us to … Comparison with ”classic” aCGH 1.Measure the gene dosage for each SNP locus  2.Identifes the genotype call for each of e.g. 250k SNP loci - A/A A/B B/B Given 1 and 2 ; differences in allele intensity can be estimated - e.g.more detailed detection of loss A/- B/- - allelic imbalance e.g. A/A/B - copy neutral LOH N: A/B T: A/A -

12. Copy neutral LOH in chromosome 14 in NBL cell line SK-N-SH CN-LOH LOH

13. 2 3 4 1 NBL case

14. 2 3 4 1

15. 2 3 4 1 LOH 111

16. 2 3 4 1 NBL case LOH 111 Comparison

17. We like to collaborate ! Research Clincal diagnostics »Contact: tommy.martinsson@gu.se

18. Acknowledgements Helena Carén Hannah Kryh Linda Olsson Jennie Erichsen Rose-Marie Sjöberg Cecilia Krona Katarina Ejeskär Susanne Fransson Frida Abel Catarina Darnfors Ylva Oleskog Maria Nethander Staffan Nilsson Jonas Abrahamsson Per Kogner