12p rearrangement and DNA amplification mapped by comparative genomic hybridization in a patient with secondary...

Rearrangements of the short arm of chromosome 12 (12p) are a common finding in hematologic malignancies. There has recently been considerable interest in chromosome 12 abnormalities in view of the mapping of the TEL gene to 12p13 and frequent 12p interstitial deletions. Overrepresentation of 12p sequences is, on the other hand, a consistent finding in testicular germ cell tumor (TGCT), and the 12p11.2-p12.1 subregion has been found to be specifically involved. We have studied a secondary leukemic patient whose cells contained 12p rearrangements with a view to clarifying the underlying molecular events. Fluorescence in situ hybridization (FISH) and comparative genomic hybridization (CGH) have revealed the presence of 12p11 breakpoints on both 12 homologs as well as amplification of 12p11-p12-derived sequences. Six YACs and a cosmid probe have been used in an attempt to map the amplification unit on 12p. The two YACs contigs WC-1468 and WC-985 were not amplified, and our results suggested a small amplicon localized in the 12p11.2-p12 subregion. We speculate that this region harbors gene(s) which are critical in tumor formation and could be involved in both TGCT and our patient. Whether the same gene(s) are involved in both amplification and translocation is unknown.