MICROSATELLITE INSTABILITY AND OTHER MOLECULAR ABNORMALITIES IN CHILDHOOD ACUTE LYMPHOBLASTIC-LEUKEMIA

Microsatellite instability (MSI) has been considered to represent the defect of DNA mismatch repair systems and has been implicated in the t umourigenesis of several human malignancies. To investigate the possib le presence of microsatellite instability in childhood acute lymphobla stic leukaemia (ALL), we examined 48 primary ALL samples. Instability was determined at 85 different microsatellite loci localized to 12 dif ferent chromosome arms. Microsatellite instability was detected in fiv e (10%) samples. Interestingly, the instability was found at chromosom al regions associated with frequent alterations. Two samples had insta bility 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 deleti on at 9p21. The fifth sample had instability at the microsatellite mar ker on 6q, which we have found is a frequent region of loss of heteroz ygosity in childhood ALL. Taken together, instability was rare in chil dhood ALL, but was localized to the three most frequently deleted chro mosome regions in childhood ALL, suggesting that localized microsatell ite instability may identify a fragile chromosomal region which could result in alteration of surrounding target genes and lead to leukaemia .