Somatic Shift to Homozygosity for a Chromosomal Polymorphism in a Child

I T HAS BECOME clear in recent years that malignant clones often exhibit chromosome abnormalities, and that these acquired abnormalities are often highly specific for a particular type of tumor. Translocations, as well as deletions of entire chromosomes or of specific regions, are well-known findings in chronic myelogenous leukemia, meningioma, and retinoblastoma, for example. Disturbances of chromosome segregation leading to loss or gain of apparently random chromosomes, and consequently to hypodiploidy or hyperdiploidy, are frequently found in acute myeloblastic leukemia (AML) and acute lymphoblastic leukemia (ALL). Other chromosomal mechanisms, leading to genetic homozygosity, have very recently been shown to be operating in retinoblastomas and Wilms’ tumors. The use ofcloned DNA probes homologous to regions of chromosome 1 3q and chromosome I I p. respectively, has shown that regions that are heterozygous in unaffected cells of individuals with tumors are homozygous in the tumor cells themselves. Mitotic nondisjunction and duplication (leading to loss of an entire chromosome, duplication of its homolog, and consequent homozygosity for the entire chromosome) as well as mitotic recombination (leading to homozygosity for only that area of the chromosome distal to the recombination event) may both play a role in this shift from genetic heterozygosity to homozygosity. We report here on a young girl with ALL who had two types of chromosome abnormalities in her malignant clone: hyperdiploidy due to tetrasomy 8, 10, and 21; and a shift from heterozygosity to homozygosity for a large chromosome polymorphism on chromosome 1 5p. To our knowledge this type of cytogenetic event has not been previously reported.