LOSS OF HETEROZYGOSITY IN THE CHROMOSOMAL REGION 12P12-13 IS VERY COMMON IN CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA AND PERMITS THE PRECISE LOCALIZATION OF A TUMOR-SUPPRESSOR GENE DISTINCT FROM P7(KIP1)

Abnormalities of the short arm of chromosome 12 are relatively common in hematologic malignancies and deletions of the region 12p12-13 are f ound in approximately 5% of the patients with acute lymphoblastic leuk emia (ALL). As a potent inhibitor of cyclin-dependent kinases, p27KIP1 prevents the progression of the cell cycle and the gene encoding p27( KIP1) represents a potential tumor-suppressor gene. Its recent assignm ent to the chromosomal region (12p12.3) prompted us to study the p27(K IP1) gene in a series of 61 children with ALL, Microsatellite polymorp hic markers flanking the p27(KIP1) gene were analyzed to detect losses of heterozygosity (LOH). Eleven patients displayed LOH for at least o ne of the markers, The deleted area encompassed the p27(KIP1) gene loc us in 10 cases, but inactivation of the remaining allele by deletion, translocation, or mutation was never observed. In addition, in 1 patie nt, the p27(KIP1) gene was situated outside of the region of LOH, Thus , p27(KIP1) does not seem to be the target gene of 12p12-13 alteration s, However, this study indicates that 12p12-13 alterations at the mole cular level, which are present in about 27% of the children with B-lin eage ALL, are much more common than had previously been reported by us ual chromosome analysis, Moreover, LOH mapping allowed us to better de fine the location of a putative tumor-suppressor gene implicated in th ese malignancies and should therefore help in identifying this gene. ( C) 1995 by The American Society of Hematology.