Aberrant methylation of imprinted genes is associated with negative hormone receptor status in invasive breast cancer

Barrow, Timothy, Barault, L, Ellsworth, RE, Harris, HR, Binder, AM, Valente, AL, Shriver, CD and Michels, KB (2015) Aberrant methylation of imprinted genes is associated with negative hormone receptor status in invasive breast cancer. International Journal of Cancer, 137 (3). pp. 537-547. ISSN 0020-7136

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Abstract

Epigenetic regulation of imprinted genes enables monoallelic expression according to parental
origin, and its disruption is implicated in many cancers and developmental disorders. The
expression of hormone receptors is significant in breast cancer as they are indicators of cancer cell
growth rate and determine response to endocrine therapies. We investigated the frequency of
aberrant events and variation in DNA methylation at nine imprinted sites in invasive breast cancer
and examined the association with estrogen and progesterone receptor status. Breast tissue and
blood from patients with invasive breast cancer (n=38) and benign breast disease (n=30) were
compared to those from healthy individuals (n=36), matched to the cancer patients by age at
diagnosis, ethnicity, BMI, menopausal status, and familial history of cancer. DNA methylation
and allele-specific expression were analyzed by pyrosequencing. Tumor-specific methylation
changes at IGF2 DMR2 were observed in 59% of cancer patients, IGF2 DMR0 in 38%, DIRAS3
DMR in 36%, GRB10 ICR in 23%, PEG3 DMR in 21%, MEST ICR in 19%, H19 ICR in 18%,
KvDMR in 8%, and SNRPN/SNURF ICR in 4%. Variation of methylation was significantly greater
in breast tissue from cancer patients than healthy individuals and benign breast disease. Aberrant
methylation of three or more sites was significantly associated with negative estrogen-alpha
(Fisher’s Exact Test, p=0.02) and progesterone-A (p=0.02) receptor status. Aberrant events and
increased variation of imprinted gene DNA methylation therefore appear to be frequent in invasive
breast cancer and are associated with negative estrogen and progesterone receptor status, without
loss of monoallelic expression.

Item Type: Article
Subjects: Sciences > Biomedical Sciences
Divisions: Faculty of Health Sciences and Wellbeing
Depositing User: Timothy Barrow
Date Deposited: 26 Feb 2018 10:01
Last Modified: 26 Feb 2018 11:12
URI: http://sure.sunderland.ac.uk/id/eprint/8780

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