Minireview: branded from the start-distinct oncogenic initiating events may determine tumor fate in the thyroid.
Thyroid follicular neoplasms commonly have aneuploidy, presumably due to chromosomal instability. This property is associated with a greater malignant potential and worse prognosis. Recently, there has been considerable progress in our understanding of mechanisms that may account for chromosomal instability in cancer cells. Many tumors with chromosomal instability have abnormalities in the cell cycle checkpoint that monitors the fidelity of mitosis. Mutations of Bub1 or BubR1, genes coding for kinases involved in mitotic spindle assembly checkpoint signaling, are found in a small subset of aneuploid tumors. Other components of protein complexes responsible for attachment of kinetochores to microtubules, or for cohesion between sister chromatids, may also be subject to alterations during tumor progression. Here, we also discuss the evidence that certain oncogenic events, such as Ras mutations, may predispose cells to chromosomal instability by favoring inappropriate posttranslational changes in mitotic checkpoint components through activation of upstream kinases during tumor initiation or progression.
Fagin
James A
JA
Division of Endocrinology and Metabolism, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0547, USA. James.Fagin@uc.edu
D000782:Aneuploidy; D002453:Cell Cycle / Q000235:genetics; D018797:Cell Cycle Proteins; D002471:Cell Transformation, Neoplastic; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D008938:Mitosis / Q000235:genetics; D009154:Mutation; D011379:Prognosis; D011494:Protein Kinases / Q000235:genetics; D017346:Protein Serine-Threonine Kinases; D013964:Thyroid Neoplasms / Q000235:genetics* / Q000473:pathology
D018797:Cell Cycle Proteins; D011494:Protein Kinases; C584277:BUB1 protein, human; C090464:Bub1 spindle checkpoint protein; D017346:Protein Serine-Threonine Kinases