Microsatellite instability and other molecular abnormalities in childhood acute lymphoblastic leukaemia.
Microsatellite instability (MSI) has been considered to represent the defect of DNA mismatch repair systems and has been implicated in the tumourigenesis of several human malignancies. To investigate the possible presence of microsatellite instability in childhood acute lymphoblastic leukaemia (ALL), we examined 48 primary ALL samples. Instability was determined at 85 different microsatellite loci localized to 12 different chromosome arms. Microsatellite instability was detected in five (10%) samples. Interestingly, the instability was found at chromosomal regions associated with frequent alterations. Two samples had instability at the microsatellite marker within the TEL gene on chromosome arm 12p. Two other samples had instability at a microsatellite marker close to CDKN2/p16 on 9p; one of these samples had a homozygous deletion at 9p21. The fifth sample had instability at the microsatellite marker on 6q, which we have found is a frequent region of loss of heterozygosity in childhood ALL. Taken together, instability was rare in childhood ALL, but was localized to the three most frequently deleted chromosome regions in childhood ALL, suggesting that localized microsatellite instability may identify a fragile chromosomal region which could result in alteration of surrounding target genes and lead to leukaemia.
Takeuchi
S
S
Division of Hematology/Oncology, Cedars-Sinai Research Institute, UCLA School of Medicine, Los Angeles, California, U.S.A.
Seriu
T
T
Tasaka
T
T
Koike
M
M
Cho
S K
SK
Park
S
S
Slater
J
J
Mufti
I
I
Hatta
Y
Y
Miyoshi
I
I
Bartram
C R
CR
Koeffler
H P
HP
D015139:Blotting, Southern; D002648:Child; D002675:Child, Preschool; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D015321:Gene Rearrangement; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D018895:Microsatellite Repeats; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics*; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D014157:Transcription Factors / Q000235:genetics*; D000097764:ETS Translocation Variant 6 Protein
D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D014157:Transcription Factors; D000097764:ETS Translocation Variant 6 Protein