Using high resolution array comparative genomic hybridisation analysis for whole genome analysis of medulloblastomas, we have identified several chromosomal aberrations. These included consistent chromosomal gains of 2p23-p25 (52.63%), 7 (57.89%), 9q34 (47.37%) and 17q11-q25 (89.47%), as well as losses of 3q25.33-q26.32 (57.9%), 4q31-33 (42.1%), 6q22-27 (57.9%), 8p21.3-23 (78.95%), 10q22-26 (57.9%), 16q22-q24 (63.16%) and 17p13 (31.6%). This information will lead to a better understanding of medulloblastoma tumorigenesis and identify new molecular markers for therapeutic intervention and drug discovery of this cancer. One of the most notable finding is detection of homozygous deletion on chromosome 6q23. Homozygous deletion of this region was found on cell line DAOY whereas copy loss was detected on 30% primary medulloblastomas. Further study using 30 pairs of STS markers confined a 0.887Mb minimal region of homozygous deletion at 6q23.1 which was flanked by markers SHGC-14149 (6q22.33) and SHGC-110551 (6q23.1). Quantitative RT-PCR analysis showed complete loss of expression of 2 genes located at 6q23.1, AK091351 (Hypothetical protein FLJ34032) and KIAA1913, on cell line DAOY. mRNA level of these genes were reduced in cell lines D283 and D384, as well as 50% (AK091351) and 70% (KIAA1913) of 10 primary tumors. Frequent detection of reduced expression of AK091351 and KIAA1913 implicated that these 2 genes may play a critical role in medulloblastoma tumorigenesis.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]