Amplified c-MYC sequences localized by fluorescence in-situ hybridization on double minute chromosomes in acute myeloid leukemias

Abstract

Double minute chromosomes (dmin) are small acentric fragments frequently observed when karyotyping human tumor cells. They are considered the cytogenetic manifestation of gene amplification. The finding of dmin in leukemia is a rare event usually associated with progression of the disease and unfavorable prognosis. We present four patients affected by myeloid disorders with an abnormal karyotype and a variable number of dmin. In an attempt to clarify the origin of the dmin and the amplified gene, we utilized a fluorescent in-situ hybridization (FISH) technique and a panel of specific probes. The results of the analysis indicate that, although chromosomes 8 are apparently uninvolved, dmin retained c-MYC sequencs in three cases. By observing previously reported cases, we found that the majority of patients with myeloid disorders and dmin showed an amplified c-MYC gene, regardless of the chromosomal abnormalities. The FISH technique proved to be informative in demonstrating gene amplification in both metaphase and interphase cells. Finally, in the one patient carrying a 20q deletion, FISH allowed the detection of a previously unreported translocation between a 16p and the 20q-, confirming the ability of the technique to understand complex karyotypes.