Epigenetic Dysregulation of KCNK9 Imprinting and Triple-Negative Breast Cancer

Autor: Kendall J. Kennedy, Carola M. Zalles, Ombeni M. Idassi, Eric C. Dietze, Dustin E. Schones, Michael N. Gould, Christopher Sistrunk, Jackelyn A. Alva-Ornelas, David K. Ann, David Skaar, Randy L. Jirtle, Victoria L. Seewaldt, Terry Hyslop, Gustavo Miranda Carboni, Adrian Ambrose
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Cancers; Volume 13; Issue 23; Pages: 6031
Cancers, Vol 13, Iss 6031, p 6031 (2021)
Cancers
ISSN: 2072-6694
DOI: 10.3390/cancers13236031
Popis: Simple Summary Genomic imprinting is an inherited form of parent-of-origin specific epigenetic gene regulation that is dysregulated by poor prenatal nutrition and environmental toxins. Here, we showed that KCNK9 is imprinted in breast tissue and identified the differentially methylated region (DMR) controlling its imprint status. Hypomethylation at the DMR, coupled with biallelic expression of KCNK9, occurred in 63% of triple-negative breast cancers (TNBC). The association between hypomethylation and TNBC status was highly significant in African-Americans (p = 0.006), but not in Caucasians (p = 0.70). The high frequency of KCNK9 DMR hypomethylation in TNBC and non-cancerous breast tissue from high-risk women provides evidence that hypomethylation of the KNCK9 DMR/TASK3 overexpression may provide a new target for prevention of TNBC. Abstract Genomic imprinting is an inherited form of parent-of-origin specific epigenetic gene regulation that is dysregulated by poor prenatal nutrition and environmental toxins. KCNK9 encodes for TASK3, a pH-regulated potassium channel membrane protein that is overexpressed in 40% of breast cancer. However, KCNK9 gene amplification accounts for increased expression in
Databáze: OpenAIRE
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