The localization of human ETS genes at the 11q23 and 21q22 regions suggested a possible involvement of these genes in both constitutional and acquired (neoplasia) diseases, presenting a known cytogenetic abnormality. The 11q23 region is involved in a number of chromosome abnormalities peculiar to acute leukemias of the myelomonocytic lineage. In two of these abnormalities, the translocations (4;11)(q21;q23) and (9;11)(p21;q23), transpositions of the ETS1 gene from its normal position on chromosome 11 to chromosomes 4 and 9, is evident. On the other hand, the 21q22 region is relevant both in human and cancer genetics. In an acquired cytogenetic abnormality specific to AML-M2 leukemias, we found ETS2 transposed from chromosome 21 to chromosome 8. Despite the repositioning of the ETS genes, neither one was found to be structurally involved by the chromosome rearrangements. The role of these genes in the pathogenesis of these leukemias is, therefore, not directly demonstrated, even if """"""""position effect,"""""""" well known to affect gene regulation at a distance, may somehow alter their expression. The real """"""""cancer genes"""""""" involved by the above-mentioned abnormalities, therefore, have to be identified. As far as the ETS2 gene is concerned, part of the work was aimed at demonstrating whether or not it does belong to the obligate genetic region necessary for the expression of the constitutional aneuploidy known as Down's syndrome. This work led to a preliminary observation, based on a singular patient sample (only very rare Down's syndrome patients are informative), that there are three copies of ETS alleles in the region. It is, therefore, possible that the ETS2 gene belongs to the set of genes needed for the expression of the multitrait Down's syndrome clinical picture.
