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- Hahn, Michael A, et al.
(författare)
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CDC73/HRPT2 CpG island hypermethylation and mutation of 5 -untranslated sequence are uncommon mechanisms of silencing parafibromin in parathyroid tumors
- 2010
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Ingår i: ENDOCRINE-RELATED CANCER. - 1351-0088. ; 17:1, s. 273-282
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Tidskriftsartikel (refereegranskat)abstract
- The tumor suppressor HRPT2/CDC73 is mutated in constitutive DNA from patients with the familial disorder hyperparathyroidism-jaw tumor syndrome and in similar to 70% of all parathyroid carcinomas. In a number of HRPT2 mutant tumors however, expression of the encoded protein parafibromin is lost in the absence of a clear second event such as HRPT2 allelic loss or the presence of a second mutation in this tumor suppressor gene. We sought to determine whether hypermethylation of a 713 bp CpG island extending 648 nucleotides upstream of the HRPT2 translational start site and 65 nucleotides into exon 1 might be a mechanism contributing to the loss of expression of parafibromin in parathyroid tumors. Furthermore, we asked whether mutations might be present in the 5-untranslated region (5-UTR) of HRPT2. We investigated a pool of tissue from 3 normal parathyroid glands, as well as 15 individual parathyroid tumor samples including 6 tumors with known HRPT2 mutations, for hypermethylation of the HRPT2 CpG island. Methylation was not identified in any specimens despite complete loss of parafibromin expression in two parathyroid carcinomas with a single detectable HRPT2 mutation and retention of the wild-type HRPT2 allele. Furthermore, no mutations of a likely pathogenic nature were identified in the 5-UTR of HRPT2. These data strongly suggest that alternative mechanisms such as mutation in HRPT2 intronic regions, additional epigenetic regulation such as histone modifications, or other regulatory inactivation mechanisms such as targeting by microRNAs may play a role in the loss of parafibromin expression.
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| 2. |
- Morokuma, Tomoki, et al.
(författare)
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Subaru FOCAS Spectroscopic Observations of High-Redshift Supernovae
- 2010
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Ingår i: Nippon Tenmon Gakkai obun kenkyu hokoku. - 0004-6264. ; 62:1, s. 19-37
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Tidskriftsartikel (refereegranskat)abstract
- We present spectra of high-redshift supernovae (SNe) that were taken with the Subaru low-resolution optical spectrograph, FOCAS. These SNe were found in SN surveys with Suprime-Cam on Subaru, the CFH12k camera on the Canada-France-Hawaii Telescope, and the Advanced Camera for Surveys on the Hubble Space Telescope. These SN surveys specifically targeted z > 1 Type la supernovae (SNe Ia). From the spectra of 39 candidates, we obtained redshifts for 32 candidates and spectroscopically identified 7 active candidates as probable SNe Ia, including one at z = 1.35, which is the most distant SN la to be spectroscopically confirmed with a ground-based telescope. An additional 4 candidates were identified as likely SNe la from the spectrophotometric properties of their host galaxies. Seven candidates are not SNe la, either being SNe of another type or active galactic nuclei. When SNe la were observed within one week of the maximum light, we found that we could spectroscopically identify most of them up to z = 1.1. Beyond this redshift, very few candidates were spectroscopically identified as SNe Ia. The current generation of super red-sensitive, fringe-free CCDs will push this redshift limit higher.
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