A novel ATIII isoform pattern which was observed in 4/80 children with acute lymphatic leukaemia (ALL) and in 1/4 children with Ewing's sarcoma, has been shown by family studies to be due to a mutant form of ATIII (AT Dublin) in the heterozygous state.
The result also distinguishes the FRA11B locus from the site of translocation at 11q23-q24 in the Ewing sarcoma- and peripheral neuroepithelioma-specific t(11;22), indicating that the chromosomes of a previously reported patient heterozygous for fra(11)(q23) did not rearrange at this fragile site to give rise to Ewing sarcoma.
However, three of three neuroepithelioma and one of two Ewing's sarcoma cell lines express IGF-I mRNA; therefore, in these tumors IGF-I may be an autocrine growth factor.
Southern analysis of DNA from one Ewing sarcoma with t[11;22][q24;q12] showed that the breakpoint on chromosome 22 is more than 15 kb 5' or 8 kb 3' from the LIF gene.
Using immunoglobulin light-chain constant region, ETS1 probes, and the technique of in situ hybridization, we previously were able to show that the constitutional and ES/NE breakpoints are different.
A child with disseminated Ewing's sarcoma underwent cytogenetic investigations which showed different structural rearrangements of chromosome 22 at diagnosis (?ring22), and at relapse [t(10;22)], but the classic translocation t(11;22) was not detectable.
Cells from a constitutional 46,XX,inv(9),t(11;22) carrier and from an ES cell line with a t(11;22) were separately fused to a hypoxanthine-guanine phosphoribosyltransferase-deficient Chinese hamster cell line (RJK88).
We found that while the dbl gene is consistently found expressed in Ewing's sarcoma as a single mRNA species, of approximately 5.0 kb, it is generally absent in two seemingly related categories of tumors, neuroblastoma and neuroepithelioma.