Frequent Loss of Heterozygosity on Chromosomes 6q, 9p, 11q or 12p in Childhood Acute Lymphoblastic Leukemia

Chromosomal abnormalities on 6q, 9p, 11q and 12p have been reported frequently in acute lymphoblastic leukemia (ALL). In order to define regions that may contain tumor suppressor genes more precisely, the loss of heterozygosity (LOH) was analyzed on respective chromosome arms in childhood ALL. Using highly informative microsatellite markers, LOH was found in 17 of 112 (15%) ALL samples on 6q; in 29 of 54 (54%) on 9p; in 14 of 112 cases (13%) on 11q; in 33 of 100 (33%) on 12p. The commonly deleted region on 6q was flanked by the markers D6S468 and D6S283/D6S449 at 6q21. In 27 of the 29 cases with LOH on 9p the critical region was characterized by D9S1747 and D9S1748. Homozygous deletions of the CDKN2/INK4A/p16 gene residing in this region were found in 14 of the 27 patients. Two cases revealed LOH at the IFNA locus. Two distinct commonly deleted regions were identified on 11q and 12p, respectively. One region at 11g22 was flanked by D11S901 and D11S1391, and the other at 11q23 by D11S614 and D11S924. On chromosome 12p, one critical region was flanked by the markers D12S77 and D12S98 including the TEL gene, and the other was localized around the p27/kipl locus. Our data narrow down regions on chromosomes 6q, 9p, l lq and 12p containing putative tumor suppressor genes which may play an important role in leukemogenesis of childhood ALL.