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Molecular evaluation of abnormalities of the short arm of chromosome I in neuroblastoma

Cytogenetic analyses have documented the consistent deletion of part of the short arm of chromosome 1 in neuroblastoma cells suggesting the presence of a suppressor gene in this chromosomal region. To determine the smallest region of deletion overlap at the molecular level on independently derived tumors and to define the location of the breakpoints more precisely, Southern analyses were performed on a somatic cell hybrid panel containing the normal and altered chromosomes 1 from seven neuroblastoma lines. By this method we were able to analyze a panel of 20 cloned sequences and two isozymes to determine the location of the breakpoints. Our findings indicate that the proximal breakpoints of chromosome 1 deletions range over a distance of more than 50 cM with the most distal deletion breakpoint occurring between MYCL1 and DIS57. In addition, using restriction fragment length polymorphisms, it was determined that in at least three of the five cell lines in which MYCL1 was deleted from a chromosome I, the gene was translocated to another chromosome thus retaining the diploid complement. We propose that the neuroblastoma susceptibility gene is located distal to MYCL1 and that there is another gene which is linked to MYCL1 that may be involved in this neoplasm.