ALTERATIONS OF CDKN2 GENE STRUCTURE IN CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA - MUTATIONS OF CDKN2 ARE OBSERVED PREFERENTIALLY IN T-LINEAGE

We analyzed homozygous deletions and mutations of the CDKN2 (p16(INK4A )/MTS1) gene, using polymerase chain reaction and Southern blot analys is, in 120 children with acute lymphoblastic leukemia (ALL). Homozygou s deletion was found in 17 of 89 (19%) precursor B-ALL patients, in 11 of 24 (46%) T-ALL patients, and in 0 of 7 other phenotype ALL patient s. After excluding 28 (23%) patients who showed a homozygous deletion of CDKN2, we found that three patients (3%) had mutation at exon 2 of CDKN2 using PCR-SSCP and sequencing strategy. One had a CGA to TGA non sense mutation (Arg to stop) at codon 72, one had a l-bp deletion at c odon 117, and the third had a 2-bp deletion at codon 70, resulting in frameshifts in the two latter patients. All three of these patients we re T phenotype ALL, and the incidence of mutation in the 24 T-ALL pati ents examined was 13%. In contrast, no mutation was detected in the re maining patients with precursor-B or other type ALL (0/96). Our result s suggest that mutational inactivation of the CDKN2 gene may contribut e to the leukemogenic growth, especially in some patients with T-ALL.