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Chromatin Accessibility differentiates Invasive Lobular from Invasive Ductal Breast cancer and Dictates Response to Endocrine Treatment

ABSTRACT: Chromatin Accessibility differentiates Invasive Lobular from Invasive Ductal Breast cancer and Dictates Response to Endocrine Treatment

PROVIDER: PRJNA639106 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR12004400.fastq.gz	Fastqsanger.gz
	SRR12004500.fastq.gz	Fastqsanger.gz
	SRR12017700_1.fastq.gz	Fastqsanger.gz
	SRR12017700_2.fastq.gz	Fastqsanger.gz
	SRR12004401.fastq.gz	Fastqsanger.gz

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Chromatin Accessibility differentiates Invasive Lobular from Invasive Ductal Breast cancer and Dictates Response to Endocrine Treatment

Project description:Chromatin Accessibility differentiates Invasive Lobular from Invasive Ductal Breast cancer and Dictates Response to Endocrine Treatment

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Chromatin Accessibility differentiates Invasive Lobular from Invasive Ductal Breast cancer and Dictates Response to Endocrine Treatment

Project description:Chromatin Accessibility differentiates Invasive Lobular from Invasive Ductal Breast cancer and Dictates Response to Endocrine Treatment

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Chromatin Accessibility differentiates Invasive Lobular from Invasive Ductal Breast cancer and Dictates Response to Endocrine Treatment

Project description:Invasive lobular breast cancer (ILC) is the second most common histological sub-type of breast cancer. Although the majority of ILC are strongly hormone receptor positive and are of low-intermediate grade, they present a number of clinical challenges. These challenges include limitations in physical exam and breast imaging for early detection, decreased response to chemotherapy and prospective evidence for differences in the benefit from specific adjuvant endocrine treatment regimens when compared to invasive ductal cancer (IDC). In addition to loss of e-cadherin, ILCs possess genetic alterations that are suggestive of a unique estrogen receptor(ER) axis, including an increase in the frequency of FOXA1 mutations and decrease in GATA3 truncating mutations. We performed a randomized Phase II clinical trial, Palbociclib and Endocrine therapy for LObular breast cancer Preoperative Study (PELOP), in which patients were stratified by histological subtype and found that the magnitude of the difference between the benefit from letrozole compared tamoxifen is significantly higher in ILC versus IDC. To elucidate the mechanism underlying this divergent response we comprehensively studied the ER axis in experimental models of ILC and IDC and clinical samples and show that ILC harbors a unique ER transcriptional axis that stems from increased FOXA1 chromatin binding and an altered chromatin state. These findings provide insights to the unique pattern of response to endocrine treatment in ILC and mechanisms of resistance to endocrine treatment, and offer new treatment strategies to improve outcomes for patients with this breast cancer subtype."

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Chromatin Accessibility differentiates Invasive Lobular from Invasive Ductal Breast cancer and Dictates Response to Endocrine Treatment

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Project description:This SuperSeries is composed of the SubSeries listed below.

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Transcription profiling of human lobular and ductal invasive carcinomas vs normal breast tissue from the same patient to identify gene expression profiles of ductal and lobular carcinomas in relation to normal ductal and lobular cells

Project description:The aim of our study was to identify gene expression profiles of ductal and lobular carcinomas in relation to normal ductal and lobular cells. We examined ten mastectomy specimens from postmenopausal breast cancer patients. Ductal and lobular tumor and normal cells were microdissected from cryosections. Fifty nanograms of total RNA were amplified and labeled by PCR and in vitro transcription. GCOS pairwise comparison algorithm and rank products have identified multiple genes that are differentially expressed in comparisons between ductal and lobular tumor and normal cell types. The results suggest that these genes are involved in epithelial-mesenchymal transition, TGFbeta and Wnt signaling. These changes are present in both tumor types but appear to be more prominent in lobular carcinomas. Ten surgical specimens obtained by mastectomy from postmenopausal patients with invasive ductal (IDC) and lobular breast (ILC) carcinomas were investigated. Of these, 5 were IDCs and 5 were ILCs. Tumor and normal tissues from the same mammary gland were identified by an experienced pathologist, snap-frozen in liquid nitrogen and stored at -80ÂºC for further analysis. Microdissection, RNA isolation, amplification, labeling and microarray analysis are described in sample definitions. Samples from particular cell types (normal ductal, normal lobular, tumor ductal, tumor lobular - 10, 10, 5, 5 samples, respectively) were considered as biological replicates and were compared in between.

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Expression data from invasive lobular carcinoma

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Project description:As part of the RATHER (RAtional THERapy for breast cancer: individualized treatment for difficult-to-treat breast cancer subtypes) consortium, expression profiling of 144 untreated primary invasive lobular carcinoma (ILC) breast cancer tissues and 15 ILC cell lines was performed using microarray. Gene expression profiling of 144 ILC breast cancers and 15 ILC cell lines

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