التفاصيل البيبلوغرافية
| العنوان: |
Whole-Organ Genomic Characterization of Mucosal Field Effects Initiating Bladder Carcinogenesis. |
| المؤلفون: |
Majewski, Tadeusz, Yao, Hui, Bondaruk, Jolanta, Chung, Woonbok, Lee, Sangkyou, Lee, June Goo, Zhang, Shizhen, Cogdell, David, Yang, Guoliang, Choi, Woonyoung, Dinney, Colin, Grossman, H. Barton, Logothetis, Christopher, Scherer, Steven E., Guo, Charles C., Zhang, Li, Wei, Peng, Weinstein, John N., Issa, Jean-Pierre, Baggerly, Keith |
| المصدر: |
Cell Reports; Feb2019, Vol. 26 Issue 8, p2241-2241, 1p |
| مستخلص: |
Summary We used whole-organ mapping to study the locoregional molecular changes in a human bladder containing multifocal cancer. Widespread DNA methylation changes were identified in the entire mucosa, representing the initial field effect. The field effect was associated with subclonal low-allele frequency mutations and a small number of DNA copy alterations. A founder mutation in the RNA splicing gene, ACIN1, was identified in normal mucosa and expanded clonally with an additional 21 mutations in progression to carcinoma. The patterns of mutations and copy number changes in carcinoma in situ and foci of carcinoma were almost identical, confirming their clonal origins. The pathways affected by the DNA copy alterations and mutations, including the Kras pathway, were preceded by the field changes in DNA methylation, suggesting that they reinforced mechanisms that had already been initiated by methylation. The results demonstrate that DNA methylation can serve as the initiator of bladder carcinogenesis. Graphical Abstract Highlights • Field change in DNA methylation is the initiator of bladder carcinogenesis • The methylation changes suppressed immunity and dysregulated Ras-related pathways • Founder ACIN1 mutation in normal mucosa clonally expanded in progression to carcinoma • Cells with mutations of 22 genes expanded clonally with progression to carcinoma Majewski et al. report that methylation changes suppressing innate immunity and dysregulating Ras-related pathways initiate bladder carcinogenesis. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
