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Identification of novel candidate target genes at 3q26.2-q29 in squamous cell carcinoma of the lung

ABSTRACT: High-resolution array-CGH was performed to identify differences in the patterns of genomic imbalances between SCC and AC of non-small cell lung cancer (NSCLC). On a genome-wide profile, SCCs showed higher frequency of gains than ACs (p = 0.067). More specifically, statistically significant differences were observed across the histologic subtypes for gains at 2q14.2, 3q26.2-q29, 12p13.2-p13.33, and 19p13.3, as well as losses at 3p26.2-p26.3, 16p13.11, and 17p11.2 in SCC, and gains at 7q22.1 and losses at 15q22.2-q25.2 occurred in AC (P < 0.05). The most striking difference between SCC and AC was gains at 3q26.2-q29, occurring in 86% (19/22) of SCCs, but in only 21% (3/14) of ACs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE16597 | GEO | 2009/06/19

SECONDARY ACCESSION(S): PRJNA116165

REPOSITORIES: GEO

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Identification of novel candidate target genes at 3q26.2-q29 in squamous cell carcinoma of the lung

Project description:High-resolution array-CGH was performed to identify differences in the patterns of genomic imbalances between SCC and AC of non-small cell lung cancer (NSCLC). On a genome-wide profile, SCCs showed higher frequency of gains than ACs (p = 0.067). More specifically, statistically significant differences were observed across the histologic subtypes for gains at 2q14.2, 3q26.2-q29, 12p13.2-p13.33, and 19p13.3, as well as losses at 3p26.2-p26.3, 16p13.11, and 17p11.2 in SCC, and gains at 7q22.1 and losses at 15q22.2-q25.2 occurred in AC (P < 0.05). The most striking difference between SCC and AC was gains at 3q26.2-q29, occurring in 86% (19/22) of SCCs, but in only 21% (3/14) of ACs. Array-CGH was performed to compare the different patterns of genetic alterations. DNA from NSCLC patients (n=36) and human reference DNA (Promega) were differentially labeled and cohybridized on the array. The Fisher exact test utilized two categories, normal and abnormal (loss and gain), with the null hypothesis that the relative proportions of each of the two imbalance categories would be expected to be the same in the groups. The counts of abnormal versus normal were summarized by subtype of NSCLC for each BAC, providing 2x2 tables for analysis. A multiple testing correction (Benjamini-Hochberg false discovery rate (FDR)) was applied to correct for the high number of false positive calls.

2010-05-18 | E-GEOD-16597 | biostudies-arrayexpress

Proteomic analysis reveals key differences between squamous cell carcinomas and adenocarcinomas across multiple tissues

Project description:To explore the biological insights into squamous cell carcinoma (SCC) derived from different organs, we reported a deep proteomic analysis of 333 SCCs of 17 organs and 69 adenocarcinomas (ACs) of 7 organs. Proteomic comparison between pan-SCCs and pan-ACs identifies distinguishable pivotal pathways, including keratinization, glucose metabolism, and extracellular matrix. Molecules in those pathways play consistent adverse or opposite prognostic roles in ACs and SCCs. A comparison between common and rare SCCs highlights lipid metabolism may reinforce the malignancy of rare SCCs. Proteomic clusters reveal anatomical features, and kinase-transcription factor networks indicate differential SCC initiation, while immune subtyping reveals diverse tumor microenvironments across and within diagnoses and identified potential druggable targets. HPV16 infected anogenital SCCs exhibit immune escape and higher inositol phosphate catabolic process. Furthermore, tumor-specific proteins provide candidates with differentially diagnostic values. This proteomics architecture represents a unique public resource for researchers seeking a better understanding of SCCs.

2022-05-19 | PXD033794 | iProX

Activation of bivalent factor DLX5 cooperates with master regulator TP63 to promote squamous cell carcinoma [RNA-Seq]

Project description:To reconstruct systematically master regulator transcription factor (MRTF)-dependent transcription networks in squamous cell carcinomas (SCCs), a novel computational method (ELMER) was applied to 1,293 pan-SCC patient samples and identified 44 hyperactive SCC MRTFs. As the top candidate, DLX5 exhibits a notable bifurcate re-configuration of its bivalent promoter in cancer. Specifically, DLX5 maintains a bivalent state in normal tissues; it undergoes de novo DNA hypermethylation and transcriptional repression in multiple non-SCC cancers. In stark contrast, DLX5 promoter gains active histone marks and becomes transcriptionally activated in SCCs, which is mediated directly by SOX2. Functionally, DLX5 is essential for SCC viability, migration, anchorage-independent growth and xenograft proliferation. Mechanistically, DLX5 interacts and cooperates with TP63 to regulate ~2,000 enhancers and promoters, which converge on activating cancer-promoting pathways. Together, our data establish a novel and strong SCC-promoting factor, and elucidate a new epigenomic mechanism - bifurcate chromatin re-configuration - during cancer development.

2021-09-14 | GSE142862 | GEO

Activation of bivalent factor DLX5 cooperates with master regulator TP63 to promote squamous cell carcinoma [ChIP-Seq]

2021-09-14 | GSE142861 | GEO

Gene expression differences between adenocarcinoma and squamous cell carcinoma in human NSCLC (qRT-PCR)

Project description:Gene expression differences between the tumor subtypes AC and SCC were analyzed using t-test. Keywords: disease subtype analysis

2009-10-01 | GSE10936 | GEO

Resident Macrophages are Locally Programmed for Silent Clearance of Apoptotic Cells

Project description:Although apoptotic cells (ACs) contain nucleic acids that can be recognized by Toll-like receptors (TLRs), engulfment of ACs does not initiate inflammation in healthy organisms. To better understand this phenomenon, we identified and characterized macrophage populations that continually engulf ACs in several distinct tissues. These macrophages share characteristics compatible with immunologically silent clearance of ACs, including high expression of AC recognition receptors, low expression of TLR9, and reduced TLR responsiveness to nucleic acids. When removed from tissues, these macrophages lose many of these characteristics and generate inflammatory responses to AC-derived nucleic acids, suggesting that cues from the tissue microenvironment are required to program macrophages for silent AC clearance. We show that KLF2 and KLF4 control expression of many genes within this AC clearance program. Coordinated expression of AC receptors with genes that limit responses to nucleic acids may represent a central feature of tissue macrophages that ensures maintenance of homeostasis.

2017-11-15 | GSE93820 | GEO

Molecular profiling of cutaneous squamous cell carcinomas and actinic keratoses from organ transplant recipients

Project description:The risk of developing cutaneous squamous cell carcinoma (SCC) is markedly increased in organ transplant recipients (OTRs) compared to the normal population. Next to sun exposure, the immunosuppressive regimen is an important risk factor for the development of SCC in OTRs. Various gene mutations (e.g. TP53) and genetic alterations (e.g. loss of CDKN2A, amplification of RAS) have been found in SCCs. The aim of this genome-wide study was to identify pathways that are consistently involved in the formation of SCCs and their precursor lesions, actinic keratoses (AKs). To perform the analysis in an isogenic background, RNA and DNA were isolated from normal (unexposed) epidermis, benign AK, and SCC from each of 15 OTRs. Hierarchical cluster analysis of mRNA expression profiles showed SCC, AK and epidermal samples to separate into three distinct groups. Several thousand genes were differentially expressed between epidermis, AK and SCC; most upregulated in SCCs were genes related to hyperproliferation and stress markers, such as keratin 6 (KRT6), KRT16 and KRT17. Matching to oncogenic pathways revealed activation of downstream targets of RAS and cMYC in SCCs and of NFkappaB and TNF already in AKs. Patients were selected from the group of OTRs that are regularly seen at the dermatology clinic of the Leiden University Medical Center. Patients with clinically suspected SCC were informed on the study and after informed consent was obtained, fresh frozen samples were obtained from SCCs (n=15), AKs (n=14) and NS (n=13). RNA was isolated and gene expression profiles were obtained using HumanWG-6 v2 Expression BeadChips (Illumina). The normalized expression data was analyzed for differences in expression between SCC, AK and NS, at single-gene level but also at geneset level.

2013-02-06 | E-GEOD-32628 | biostudies-arrayexpress

ArrayCGH mapping of chromosome 3 aberrations in lung Squamous Cell Carcinoma (SCC)

Project description:To prospectively identify new oncogenes implicated in lung Squamous Cell Carcinoma pathogenesis, we investigated chromosome 3 aberrations in advanced tumours using arrayCGH. These aberrations are indeed among the most frequent aberrations in lung SCC and correlate with SCC patient's poor prognosis. We precisely map regions of recurrent losses at 3p and gains at 3q25-qter in a series of lung SCC. We moreover uncover 3q26.3-q27 high level amplifications in 20% of tumours. Keywords: ArrayCGH, Lung Squamous Cell Carcinoma, 3q26.3, SOX2

2010-02-10 | GSE14859 | GEO

Chromosomal aberration of ESCC and HSCC cell lines

Project description:In order to identify putative targets in squamous cell carcinoma (SCC), a survey of parallel chromosomal alterations and gene expression studies in 10 SCC cell lines were performed using array-CGH and microarray techniques. The most frequent changes were gains of 11q13.1-13.3 and losses of 18q12.1-23 in SCC. Furthermore, the expression levels of the sets of genes at both these loci in SCC were measured using microarray analysis. By combining the array-CGH with the microarray data, 10 genes at 11q13.1-13.3 and 6 genes at 18q12.1-23 whose expression correlated with chromosomal alterations were identified. Keywords: comparative genomic hybridization

2008-12-01 | GSE11938 | GEO

ArrayCGH mapping of chromosome 3 aberrations in lung Squamous Cell Carcinoma (SCC)

2010-05-14 | E-GEOD-14859 | biostudies-arrayexpress

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