| Budget Amount *help |
¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2012: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
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| Outline of Final Research Achievements |
We confirmed intratumoral overproduction of PTH, but not PTHrP, in a retroperitoneal malignant fibrous hyperplasia in a patient who showed lethal hypercalcemia by using RT-PCR and immunohistochemical assay. The rearrangements or mutations of the PTH gene were not observed, while several transcriptional factors responsible for PTH gene regulation were markedly affected in their amounts. Our RNA-seq revealed that copy number variation of chromosome 11 where PTH gene resides occurred much more frequently than that in other chromosomes. Further, we found nonsense mutations of ATRX, med1 and USP24 and so on. Lastly, we found that CYP24A1 mRNA was drastically upregulated, suggesting that resultant intratumoral hypovitaminosis D might lead to uncontrollable intratumoral overproduction of PTH protein. Additional oncogenic stimuli such as perturbations of ATRX or med1/USP24 may well resulted in ectopic PTH overproduction.
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