HIGH-RESOLUTION ALLELOTYPE ANALYSIS OF CHILDHOOD B-LINEAGE ACUTE LYMPHOBLASTIC-LEUKEMIA

Knowledge of the patterns of allelic loss has been useful in identifyi ng tumor suppressor genes in many solid tumors. Although the loss of g enetic material in acute lymphoblastic leukemias has been documented b y cytogenetic studies and microsatellite typing, a global overview of losses of heterozygosity occurring throughout the genome was not yet a vailable. We have performed a high resolution allelotype analysis in 6 3 childhood B-lineage acute lymphoblastic leukemia. A total of 247 mic rosatellite markers, evenly distributed along the autosomes were typed in blast and in remission samples from every patient. An average of 4 1 patients were informative for each marker. LOH at one or several loc i was observed in 41 of the 63 patients (64%). The mean values for the fractional allelic loss (FAL) and the hemizygosity index, calculated for each patient, were 0.03 (range 0 to 0.23) and 0.024 (range 0 to 0. 18), respectively. The most frequently involved chromosomal arms were 9p (36%), 12p (31%), 20q (15%), 6q (12%), 5p (10%) and 10p (10%). Thre e regions on chromosomal arms 9p, 12p and 6q were previously identifie d as the targets of recurring deletions, the target genes being identi fied for two of them (9p and 12p). The three new regions defined by th is allelotype may contain tumor-suppressor genes implicated in the ini tiation or progression of childhood B-ALLs.