소아 급성 백혈병의 CDKN2 (p16-INK4A/MTS1) 유전자의 돌연변이 양상

Abstract

Purpose: The human chromosome 9p21 region that is a frequent site of deletions and rearrangements in many tumor types including leukemias implied the existence of a tumor suppressor gene within 9p21 which is involved in tumor formation. CDKN2 (p16) gene is located in the same chromosomal region. The loss of CDKN2 function is probably one of the most common genetic alterations and is now thought to play a key role in leukemogenesis. We examined the frequency of the point mutation of CDKN2 gene by analyzing the DNA sequence and demonstrated the prognostic implication of mutations of CDKN2 gene in childhood acute leukemia. Methods: We investigated the prevalence of the point mutation in thirty patients with 20 cases of acute lymphoblastic leukemia (ALL) and 10 cases of acute myeloid leukemia (AML). The point mutation of CDKN2 gene was analyzed in a PCR generated DNA sequencing technique. Results: There was no point mutation in exon 1 of CDKN2 gene. A missense mutation (G→A transition) at nucleotide 364 of this gene was present in codon 122 in one T-cell ALL patient and resulted in an amino acid change from glycine to arginine. Conclusion: The point mutation of CDKN2 gene was a rare event in childhood acute leukemia, but the inactivation of this gene plays an important role in the pathogenesis of T-cell ALL. Further study is needed in more cases of acute leukemia to evaluate the prognostic significance of the alteration of CDKN2 gene in ALL.