Breakpoint characterization of the ret/PTC oncogene in human papillary thyroid carcinoma.
The ret/PTC oncogene, rearranged form of the ret proto-oncogene (c-ret), has been detected specifically in a minority of papillary thyroid carcinomas. Three forms of the ret/PTC oncogene have been identified; the two most common forms, ret/PTC-1 and ret/PTC-3, both result from a paracentric inversion, of the long arm of chromosome 10. In this study, we have successfully amplified the chimeric introns resulting from these inversions, ranging from 1.4 to 10 kb, from four of five tumors known to contain the ret/PTC-1 oncogene (where c-ret rearranges with the H4 gene), and from 1/1 tumors containing the ret/PTC-3 oncogene (where c-ret rearranges with the ele1 gene). We localized the breakpoints within the chimeric introns using nested PCR, and determined the exact nucleotide sequence at the breakpoint for each tumor. Our results indicate that the breakpoints in c-ret occur at sites distributed across intron 11, where breaks in H4 intron 1 appear more frequently at the 5'- end of the intron. Interestingly, in all tumors that we investigated, the breakpoints occurred at sits of two or three nucleotide matches between the contributing germline sequences. In summary, we describe a simple, convenient way to investigate the ret/PTC breakpoints, and have revealed several common features of the breakpoints which warrant further investigations.
Smanik
P A
PA
Department of Physiology and Internal Medicine, Ohio State University, Columbus 43210, USA.
Furminger
T L
TL
Mazzaferri
E L
EL
Jhiang
S M
SM
D001483:Base Sequence; D002291:Carcinoma, Papillary / Q000235:genetics*; D002874:Chromosome Mapping; D004273:DNA, Neoplasm / Q000235:genetics; D029721:Drosophila Proteins; D015321:Gene Rearrangement / Q000235:genetics*; D006801:Humans; D007438:Introns; D008969:Molecular Sequence Data; D015513:Oncogene Proteins / Q000235:genetics*; D015514:Oncogene Proteins, Fusion; D009857:Oncogenes; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D013964:Thyroid Neoplasms / Q000235:genetics*
D004273:DNA, Neoplasm; D029721:Drosophila Proteins; C000715470:MAS1 protein, human; D015513:Oncogene Proteins; D015514:Oncogene Proteins, Fusion; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D011505:Protein-Tyrosine Kinases; D051096:Proto-Oncogene Proteins c-ret; D020794:Receptor Protein-Tyrosine Kinases; C416649:Ret protein, Drosophila; C093573:ret-PTC fusion oncoproteins, human