MICROSATELLITE ANALYSIS OF LOSS OF HETEROZYGOSITY ON CHROMOSOMES 9Q, 11P AND 17P IN MEDULLOBLASTOMAS

Medulloblastoma (MB) is a primitive neuroectodermal tumour of the cerebellum whose pathogenesis is poorly understood. Previous studies suggest a role for loci on chromosomes 11p and 17p in the pathogenesis of MB. Evidence for another potential MB locus has recently emerged from studies on Gorlin syndrome (GS), an autosomal dominant syndrome with multiple basal cell carcinomas. epithelial jaw cysts, and skletal anomalies. Since GS can be associated with MB, we examined sporadic (non-GS) cases of MB for evidence of loss of heterozygosity (LOH) on chromosome 9 where a putative GS locus has been localized to band q31. Nineteen paired blood and MB DNA specimens from 16 patients (11 primary tumours. two primary with recurrent tumours, one primary tumour and cell line, two cell lines) were studied by PCR analysis of microsatellites at D9S55 (9p12), D9S15 (9q13-q21.1), D9S127 (9q21.1-21.3), D9Sl2 (9q22.3), D9S58 (9q22.3-q31), D9S109 (9q31), D9S53 (9q31), GSN (9q33). D9S60 (9q33-q34), D9S65 (9q33-q34), ASS (9q34). D9S67 (9q34.3), TH (11p15.5) D11S490 (11q23.3), D17S261 (17p11.2-12), D17S520 (17p12), TP53 (17pl3.1), D17S5 (17p13.3), D17S515 (17q22-qter), and by RFLP analysis at the WT-1 locus (11p13). Only two tumours had LOH on 9q. One was non-informative at D9S15, D9S65, and GSN but showed LOH at D9S127, D9S12, D9S58, D9S109, D9S53, D9S60, ASS, and D9S67. The other was uninterpretable at D9S65 and non-informative at D9S15, D9S58, D9S53. and D9S67 but exhibited LOH at D9S127, D9S12, D9S109, GSN, D9S60, and ASS, Both these cases were informative at D9S55 without LOH. These results are compatible with loss of most if not all of one copy of 9q in both tumours. None of the 19 specimens had LOH on 11p. Seven tumours showed LOH on 17p including four with LOH at all four 17p loci examined. None of the tumours with LOH on 9q had LOH on 17p and vice-versa. These data suggest that LOH on 9q occurs rarely in sporadic MB. This does not rule out a role for the GS locus in sporadic MB but makes it less likely.