Two rearranged MET alleles in MNNG-HOS cells reveal the orientation of MET on chromosome 7 to other markers tightly linked to the cystic fibrosis locus.

We have found that two alleles of the MET locus are rearranged in the human cell line MNNG-HOS. One allele is the previously characterized TPR-MET oncogene and the other is found on a der(7)t(1;7)(q23;q32) marker chromosome. These data and in situ chromosomal hybridization analysis would indicate that MET and, therefore, the cystic fibrosis locus are located at bands q31-q32 on human chromosome 7. Using somatic cell hybrids, we show that the chromosome containing the TPR-MET oncogene is grossly rearranged and contains both the upstream and downstream portions of the MET protooncogene locus. These results demonstrate that the TPR-MET oncogene rearrangement involving chromosomes 1 and 7 is either due to an insertion of TPR sequences into the MET locus or is more complex. We also show that the upstream MET protooncogene locus is deleted on der(7), while the downstream portion is retained. We cannot exclude that this is due to an interstitial chromosomal deletion or to a more complex rearrangement, but if MET maps at the breakpoint in der(7), then the 3' end of the MET transcription unit should be oriented towards the centromere. We also show that other DNA restriction fragment length polymorphism markers tightly linked with the inheritance of cystic fibrosis are deleted on der(7).