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Gene signature driving invasive mucinous adenocarcinoma of the lung

ABSTRACT: Gene signature driving invasive mucinous adenocarcinoma of the lung

PROVIDER: PRJNA343081 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR4244280.fastq.gz	Fastqsanger.gz
	SRR4244290.fastq.gz	Fastqsanger.gz
	SRR4244300.fastq.gz	Fastqsanger.gz
	SRR4244300_1.fastq.gz	Fastqsanger.gz
	SRR4244300_2.fastq.gz	Fastqsanger.gz

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Project description:Mucinous colorectal adenocarcinoma

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Gene signature driving invasive mucinous adenocarcinoma of the lung.

Project description:Though invasive mucinous adenocarcinoma of the lung (IMA) is pathologically distinctive, the molecular mechanism driving IMA is not well understood, which hampers efforts to identify therapeutic targets. Here, by analyzing gene expression profiles of human and mouse IMA, we identified a Mucinous Lung Tumor Signature of 143 genes, which was unexpectedly enriched in mucin-producing gastrointestinal, pancreatic, and breast cancers. The signature genes included transcription factors FOXA3, SPDEF, HNF4A, mucins MUC5AC, MUC5B, MUC3, and an inhibitory immune checkpoint VTCN1/B7-H4 (but not PD-L1/B7-H1). Importantly, induction of FOXA3 or SPDEF along with mutant KRAS in lung epithelium was sufficient to develop benign or malignant mucinous lung tumors, respectively, in transgenic mice. FOXA3 and SPDEF induced MUC5AC and MUC5B, while HNF4A induced MUC3 in human mucinous lung cancer cells harboring a KRAS mutation. ChIP-seq combined with CRISPR/Cas9 determined that upstream enhancer regions of the mucin genes MUC5AC and MUC5B, which were bound by SPDEF, were required for the expression of the mucin genes. Here, we report the molecular signature and gene regulatory network driving mucinous lung tumors.

| S-EPMC5376761 | biostudies-literature

Gene signature driving invasive mucinous adenocarcinoma of the lung

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

2017-03-02 | GSE86959 | GEO

High-resolution genome-wide copy number analysis of pre-invasive mucinous ovarian tumours

Project description:Introduction: Mucinous tumors are the second most common form of epithelial ovarian tumor, yet the cell of origin for this histological sub-type remains undetermined. While these tumors are thought to arise through a stepwise progression from benign cystadenoma to borderline tumor to invasive carcinoma, few studies have attempted to comprehensively characterize the genetic changes specific to this subtype or its precursors. Methods: To explore the spectrum of genomic alterations common to mucinous tumors we performed high resolution genome-wide copy number analysis, mutation screening by Sanger sequencing and immunohistochemistry on a series of primary ovarian mucinous cystadenomas (n=20) and borderline tumors (n=22). Results: Integration of copy number data, targeted mutation screening of RAS/RAF pathway members and immunohistochemistry reveals that p16 loss and RAS/RAF pathway alterations are highly recurrent events that occur early during mucinous tumor development. The frequency of concurrence of these events was observed in 40% of benign cystadenomas and 68% of borderline tumors. Conclusions: This study is the largest and highest resolution analysis of mucinous benign and borderline tumors performed to date and provides strong support for these lesions being precursors of primary ovarian mucinous adenocarcinoma. The high level of uniformity in the molecular events underlying the pathogenesis of mucinous ovarian tumors provides an opportunity for treatments targeting specific mutations and pathways. Copy number data was generated for 42 mucinous ovarian tumours (20 benign, 22 borderline). Epithelial and stromal DNA from the tumours and matched-normal lymphocyte DNA were all analysed. Processed/normalized data for the germline DNA samples are not provided because they themselves are normalised to a diploid copy number, making all the probe values 2, which is not informative.

2012-08-26 | E-GEOD-39076 | biostudies-arrayexpress

High-resolution genome-wide copy number analysis of pre-invasive mucinous ovarian tumours

2012-08-26 | GSE39076 | GEO

Transcriptome of invasive mucinous adnocarcinoma of the lung and adjacent normal lung tissues from 6 patients based on RNA-seq method

Project description:In order to identify genes that are highly expressed in human IMA, we performed mRNA-seq analysis using RNAs extracted from 6 human invasive mucinous adenocarcinoma of the lung (IMA) and adjacent normal lung tissues and determined genes differentially expressed in human IMA.

2017-03-02 | GSE86958 | GEO

Spatial transcriptomics reveals functional compartmentalization of mucinous colorectal adenocarcinoma

Project description:Spatial transcriptomics reveals functional compartmentalization of mucinous colorectal adenocarcinoma

| PRJNA992207 | ENA

Intercepting progression from pre-invasive to invasive lung adenocarcinoma

Project description:Intercepting progression from pre-invasive to invasive lung adenocarcinoma

| PRJNA808146 | ENA

Intercepting progression from pre-invasive to invasive lung adenocarcinoma

Project description:Intercepting progression from pre-invasive to invasive lung adenocarcinoma

| PRJNA808147 | ENA

Expression data from Columbia Lung Adenocarcinoma Human Tumor Cells

Project description:The World Health Organization has subclassified adenocarcinoma based upon predominant cell morphology and growth pattern such as bronchioloalveolar carcinoma (BAC), adenocarcinoma with mixed subtypes (AC-mixed), and homogenously invasive tumors with a variety of histological patterns Pure invasive adenocarcinomas are often devoid of bronchioloalveolar morphology. The clinical importance of lung adenocarcinoma invasion is supported by several recent studies indicating that the risk of death in non-mucinous BAC is significantly lower than that of pure invasive tumors and in tumors with greater than 0.6 cm of fibrosis or linear invasion (J Thorac Oncol 6:244-285) To identify human tumor cell signatures associated with lung adenocarcinoma subtype and invasion, we performed microarray gene expression profiling of microdissected tumor cells noninvasive AC and AC-Mixed invasive tumors. 17 cases of noninvasive AC tumors and 23 cases of AC-mixed subtype invasive lung adenocarcinomas resected from 2002 to 2006 were examined (Columbia Lung Adenocarcinoma dataset)

2011-09-14 | E-GEOD-27716 | biostudies-arrayexpress

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