Kinase expression and chromosomal rearrangements in papillary thyroid cancer tissues: investigations at the molecular and microscopic levels.
Structural chromosome aberrations are known hallmarks of many solid tumors. In the papillary form of thyroid cancer (PTC), for example, activation of the receptor tyrosine kinase (RTK) genes, ret or the neurotrophic tyrosine kinase receptor type I (NTRK1) by intra- or interchromosomal rearrangements have been suggested as a cause of the disease. The 1986 accident at the nuclear power plant in Chernobyl, Ukraine, led to the uncontrolled release of high levels of radioisotopes. Ten years later, the incidence of childhood papillary thyroid cancer (chPTC) near Chernobyl had risen by two orders of magnitude. Tumors removed from some of these patients showed aberrant expression of the ret RTK gene due to a ret/PTC1 or ret/PTC3 rearrangement involving chromosome 10. However, many cultured chPTC cells show a normal G-banded karyotype and no ret rearrangement. We hypothesize that the "ret-negative" tumors inappropriately express a different oncogene or have lost function of a tumor suppressor as a result of chromosomal rearrangements, and decided to apply molecular and cytogenetic methods to search for potentially oncogenic chromosomal rearrangements in Chernobyl chPTC cases. Knowledge of the kind of genetic alterations may facilitate the early detection and staging of chPTC as well as provide guidance for therapeutic intervention.
Weier
H-U G
HU
Life Sciences Division, University of California, E.O. Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA. ugweier@lbl.gov
Kwan
J
J
Lu
C-M
CM
Ito
Y
Y
Wang
M
M
Baumgartner
A
A
Hayward
S W
SW
Weier
J F
JF
Zitzelsberger
H F
HF
D000818:Animals; D002291:Carcinoma, Papillary / Q000201:enzymology* / Q000648:ultrastructure; D002460:Cell Line; D017690:Cell Transplantation; D047852:Chernobyl Nuclear Accident; D002869:Chromosome Aberrations; D002875:Chromosomes / Q000648:ultrastructure*; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D003001:Cloning, Molecular; D015342:DNA Probes; D005434:Flow Cytometry; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007621:Karyotyping; D051379:Mice; D011494:Protein Kinases / Q000096:biosynthesis*; D020794:Receptor Protein-Tyrosine Kinases / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013964:Thyroid Neoplasms / Q000201:enzymology* / Q000648:ultrastructure; D014178:Translocation, Genetic
D015342:DNA Probes; D011494:Protein Kinases; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA