Epigenome analysis of primary breast cancer tumors and different types of recurrences.
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE44870 | GEO | 2013/12/24
SECONDARY ACCESSION(S): PRJNA192598
REPOSITORIES: GEO
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Project description:Genome wide DNA methylation profiling of primary breast cancer tumors and their axillary metastasis and/or ipsilateral breast recurrence and/or contralateral breast recurrence. The Illumina Infinium 27k Human DNA methylation Beadchip v1.2 was used to obtain DNA methylation profiles across approximately 27,000 CpGs. Samples included 20 primary breast tumors and their matched axillary metastasis, 17 primary breast tumors and their matched ipsilateral breast recurrence, and 11 primary breast tumors and their matched contralateral breast recurrence. Bisulphite converted DNA from the 96 samples were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2 contributed by Institut Curie - Fabien Reyal
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Project description:The lymphatic system is a common avenue for the spread of breast cancer cells and dissemination through it occurs at least as frequently as hematogenous metastasis. Approximately 75% of primary breast cancers are estrogen receptor (ER) positive and the majority of these maintain receptor expression as lymph node (LN) metastases. However, it is unknown if ER function is equivalent in cancer cells growing in the breast and in the LNs. We have developed a model to assess estrogen responsiveness in ER(+) breast tumors and LN metastases. Fluorescent ER(+) MCF-7 tumors were grown in ovariectomized nude mice supplemented with estradiol. Once axillary LN metastasis arose, estradiol was withdrawn (EWD), for 1 or 4 weeks, or continued, to assess estradiol responsiveness. On EWD, proliferation rates fell similarly in tumors and LN metastases. However, estradiol-dependent ER down-regulation and progesterone receptor induction were deficient in LN metastases, indicating that ER-dependent transcriptional function was altered in the LN. Cancer cells from estradiol-treated and EWD primary tumors and matched LN metastases were isolated by laser capture microdissection. Global gene expression profiling identified transcripts that were regulated by the tissue microenvironment, by hormones, or by both. Interestingly, numerous genes that were estradiol regulated in tumors lost estradiol sensitivity or were regulated in the opposite direction by estradiol in LN metastases. We propose that the LN microenvironment alters estradiol signaling and may contribute to local antiestrogen resistance. Keywords: Breast cancer lymph node metastasis, ER positive, MCF7, xenograft
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