Inverse correlation between loss of heterozygosity of the short arm of chromosome 12 and p15ink4B/p16ink4 gene inactivation in childhood acute lymphoblastic leukaemia.
Seventy-four patients with acute lymphoblastic leukaemia (ALL) were analysed with limited allelotyping to detect loss of heterozygosity on chromosome segments 6q, 9p, 12p and 13q in order to detect patterns of genetic alteration. In the case of chromosome 9, analyses were also performed to detect inactivation of the p15ink4B and p16ink4 genes by Southern blot and sequencing techniques. The deletion data from these chromosomes were correlated to each other and to clinical features including prognosis. Allelic loss of these chromosomal regions could be detected in 24% (6q), 15% (12p) and 10% (13q) of the patients respectively, whereas aberrations involving 9p were detected in approximately 50% of the cases. There was an inverse correlation between loss of heterozygosity (LOH) for chromosome 12 and inactivation of the p16ink4 gene. This finding may suggest that a leukaemogenic event on chromosome 12p affects the same pathway of cell-cycle control as p16ink4 inactivation or, alternatively, reflects the fact that these mutations tend to occur in cells of different lineages.
Heyman
M
M
Radiumhemmet, Karolinska Hospital, Stockholm, Sweden.
Calero Moreno
T
T
Liu
Y
Y
Grandér
D
D
Rasool
O
O
Borgonova-Brandter
L
L
Merup
M
M
Söderhäll
S
S
Einhorn
S
S
D015139:Blotting, Southern; D002352:Carrier Proteins / Q000235:genetics; D018797:Cell Cycle Proteins; D002648:Child; D002675:Child, Preschool; D002881:Chromosomes, Human, Pair 12; D002882:Chromosomes, Human, Pair 13; D002896:Chromosomes, Human, Pair 6; D002899:Chromosomes, Human, Pair 9; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004791:Enzyme Inhibitors; D017353:Gene Deletion; D006579:Heterozygote; D006801:Humans; D018895:Microsatellite Repeats; D009154:Mutation; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D025521:Tumor Suppressor Proteins
C493966:CDKN2B protein, human; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D004791:Enzyme Inhibitors; D025521:Tumor Suppressor Proteins