| 1. |
- Försti, Asta, et al.
(författare)
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Genetic variation in the major mitotic checkpoint genes associated with chromosomal aberrations in healthy humans
- 2016
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Ingår i: Cancer Letters. - : Elsevier BV. - 0304-3835. ; 380:2, s. 442-446
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Tidskriftsartikel (refereegranskat)abstract
- Non-specific chromosomal aberrations (CAs) are microscopically detected in about 1% of lymphocytes drawn from healthy persons. Causes of CAs in general population are not known but they may be related to risk of cancer. In view of the importance of the mitotic checkpoint machinery on maintaining chromosomal integrity we selected 9 variants in main checkpoint related genes (BUB1B, BUB3, MAD2L1, CENPF, ESPL1/separase, NEK2, PTTG1/securin, ZWILCH and ZWINT) for a genotyping study on samples from healthy individuals (N = 330 to 729) whose lymphocytes had an increased number of CAs compared to persons with a low number of CAs. Genetic variation in individual genes played a minor importance, consistent with the high conservation and selection pressure of the checkpoint system. However, gene pairs were significantly associated with CAs: PTTG1-ZWILCH and PTTG1-ZWINT. MAD2L1 and PTTG1 were the most common partners in any of the two-way interactions. The results suggest that interactions at the level of cohesin (PTTG1) and kinetochore function (ZWINT, ZWILCH and MAD2L1) contribute to the frequency of CAs, suggesting that gene variants at different checkpoint functions appeared to be required for the formation of CAs.
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| 2. |
- Vymetalkova, Veronika, et al.
(författare)
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Epigenome-wide analysis of DNA methylation reveals a rectal cancer-specific epigenomic signature
- 2016
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Ingår i: Epigenomics. - London, United Kingdom : Future Medicine Ltd.. - 1750-1911 .- 1750-192X. ; 8:9, s. 1193-1207
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim of the present study is to address a genome-wide search for novel methylation biomarkers in the rectal cancer (RC), as only scarce information on methylation profile is available.Materials and methods: We analyzed methylation status in 25 pairs of RC and adjacent healthy mucosa using the Illumina Human Methylation 450 BeadChip.Results: We found significantly aberrant methylation in 33 genes. After validation of our results by pyrosequencing, we found a good agreement with our findings. The BPIL3 and HBBP1 genes resulted hypomethylated in RC, whereas TIFPI2, ADHFE1, FLI1 and TLX1 were hypermethylated. An external validation by TCGA datasets confirmed the results.Conclusion: Our study, with external validation, has demonstrated the feasibility of using specific methylated DNA signatures for developing biomarkers in RC.
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