Amplification at 12q13—14 in Human Malignant Gliomas Is Frequently Accompanied by Loss of Heterozygosity at Loci Proximal and Distal to the Amplification Site1

We haverecentlyreportedthat a subsetof humanmalignantgliomas showsamplificationand overexpa-essionf multiplegenesfrom chromo somalsegment12q13-14,includingCDK4,SAS,andMDM2. In the pro sent study we have performed an allelotyping for 16 polymorphIc loci spanning both arms of chromosome 12 In a series of 136 gliomas. Allelic deletions were found in 50% (7 of 14) of the malignant gliomas with 12q13-14 amplification and Involved loci located on 12q proximal and distalto theamplificationsite.In contrast,theIncidenceof alleliclosson chromosome12 was significantlylower in gliomaswithout 12q13-14 amplification [14% (11 of 79) In the WHO grade ifi and IV gliomas, 9% (4 of 43) in the WHO gradeI and II gliomas].The frequentassociation between 12q13-14 amplification and loss ofalleles from 12q Is in line with a model suggestingchromosomebreakageand deletionas Important events In the development of gene amplification.