Mutational Analysis of the Candidate Tumor Suppressor Genes

We have shown previously that loss of heterozygosity at chromosome band 12pl3 is among the most frequent genetic abnormalities identified in acute lymphoblastic leukemia (ALL) of childhood. Two known genes map within the critically deleted region of 12p: '/'/•'/.. the gene encoding a new member of the ETS family of transcription factors, which is rearranged in a variety of hematological malignancies; and A//'/, the gene encoding the cyclin-dependent kinase inhibitor p27. Both genes are, therefore, excellent candidate tumor suppressor genes. In this report, we determined the exon organization of the '/'/•.'/. gene and performed mutational analysis of '/'/•.'/. and KIP1 in 33 childhood ALL patients known to have loss of heterozy gosity at this locus. No mutations in either TEL or K1P1 were found; this suggests that neither TEL nor KIP1 is the critical 12p tumor suppressor gene in childhood ALL.