Dicer sequencing, whole genome methylation profiling and RNA sequencing analysis in basal cell carcinoma [RNA-seq]
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE128786 | GEO | 2019/10/25
REPOSITORIES: GEO
Similar Datasets
Project description:Dicer sequencing was performed on the Illumina MiSeq System in a total of 16 BCC samples (8 nodular BCCs / 8 sBCCs) and mapped against the human reference genome (hg19). Dicer sequencing was performed in all 16 BCC samples. Whole genome methylation profiling performed with Infinium MethylationEPIC BeadChips as well as RNA and smallRNA sequencing were performed in 5 sBCCs with the Illumina NextSeq500 next generation sequencing system. We identified a variety of Dicer mutations that could play a role in aberrant miRNA expression in BCC. The aforementioned RNA sequences should be further evaluated in functional studies towards their possible pathogenetic role in sBCC.
2019-10-25 | GSE128789 | GEO
Project description:Dicer sequencing was performed on the Illumina MiSeq System in a total of 16 BCC samples (8 nodular BCCs / 8 sBCCs) and mapped against the human reference genome (hg19). Dicer sequencing was performed in all 16 BCC samples. Whole genome methylation profiling performed with Infinium MethylationEPIC BeadChips as well as RNA and smallRNA sequencing were performed in 5 sBCCs with the Illumina NextSeq500 next generation sequencing system. We identified a variety of Dicer mutations that could play a role in aberrant miRNA expression in BCC. The aforementioned RNA sequences should be further evaluated in functional studies towards their possible pathogenetic role in sBCC.
2019-10-25 | GSE128783 | GEO
Project description:Basal cell carcinomas (BCCs) are the most common cancers in the US. Histologic appearance distinguishes several subtypes, each of which can have a different biologic behavior. In this study global miRNA expression was quantified by high throughput sequencing in nodular BCCs, a subtype that is slow growing, and infiltrative BCCs, aggressive tumors that extend through the dermis and invade structures such as cutaneous nerves. Principal components analysis correctly classified seven out of eight infiltrative tumors on the basis of miRNA expression. The remaining tumor, on pathology review, contained a mixture of nodular and infiltrative elements. Nodular tumors did not cluster tightly, likely reflecting broader histopathologic diversity in this class, but trended toward forming a group separate from infiltrative BCCs. qPCR assays were developed for six of the miRNAs that showed significant differences between the BCC subtypes, and five of these six were validated in a replication set of four infiltrative and three nodular tumors. The expression level of miR-183, a miRNA that inhibits invasion and metastasis in several types of malignancies, was consistently lower in infiltrative than nodular tumors and could be one element underlying the difference in invasiveness. These results represent the first miRNA profiling study in BCCs and demonstrate that miRNA gene expression may be involved in tumor pathogenesis and particularly in determining the aggressiveness of these malignancies. Total RNA was extracted from eight nodular and eight infiltrative basal cell carcinomas. miRNA was then processed into libraries using the Illumina Small RNA Ver 1.5 protocol. Samples were then sequenced on the Illumina GAII system
2012-02-01 | E-GEOD-33665 | biostudies-arrayexpress
Project description:Basal cell carcinomas (BCCs) are the most common cancers in the US. Histologic appearance distinguishes several subtypes, each of which can have a different biologic behavior. In this study global miRNA expression was quantified by high throughput sequencing in nodular BCCs, a subtype that is slow growing, and infiltrative BCCs, aggressive tumors that extend through the dermis and invade structures such as cutaneous nerves. Principal components analysis correctly classified seven out of eight infiltrative tumors on the basis of miRNA expression. The remaining tumor, on pathology review, contained a mixture of nodular and infiltrative elements. Nodular tumors did not cluster tightly, likely reflecting broader histopathologic diversity in this class, but trended toward forming a group separate from infiltrative BCCs. qPCR assays were developed for six of the miRNAs that showed significant differences between the BCC subtypes, and five of these six were validated in a replication set of four infiltrative and three nodular tumors. The expression level of miR-183, a miRNA that inhibits invasion and metastasis in several types of malignancies, was consistently lower in infiltrative than nodular tumors and could be one element underlying the difference in invasiveness. These results represent the first miRNA profiling study in BCCs and demonstrate that miRNA gene expression may be involved in tumor pathogenesis and particularly in determining the aggressiveness of these malignancies.
2012-02-01 | GSE33665 | GEO
Project description:Basal cell carcinoma (BCC) is the most frequently diagnosed skin cancer and the most common malignancy in humans. Different morphological subtypes of BCC are associated with low- or high-risk of recurrence and aggressiveness, but the underlying biology of how the individual subtypes arise remains largely unknown. Because the majority of BCCs appear to arise from mutations in the same pathway, we hypothesized that BCC development, growth and invasive potential is also influenced by the tumor microenvironment and in particular by cancer-associated fibroblasts (CAFs) and their secreted factors. In this work, we aimed to characterize the stroma of the different BCC subtypes with a focus on CAF populations. To investigate the stromal features of the different BCC subtypes, we applied laser-capture microdissection (LCM) followed by RNA sequencing. A cohort of 15 BCC samples from 5 different “pure” subtypes (superficial, nodular, micronodular, sclerosing and basosquamous; n=3 each) were selected and included in the analysis. Healthy skin was used as a control (n=6). We show that the stroma of the different BCC subtypes have distinct gene expression signatures. Nodular and micronodular seem to have the most similar signatures, while superficial and sclerosing the most different. By comparing low- and high-risk BCC subtypes, we observed that Collagen 10A1 (COL10A1) is overexpressed in the stroma of sclerosing/infiltrative and basosquamous but not micronodular high-risk subtypes. Those findings were confirmed by immunohistochemistry in a cohort of 89 different BCC and 13 healthy skin samples. Moreover, scRNAseq analysis of BCCs of two independent datasets showed that the COL10A1-expressing population of cells is associated with the stroma adjacent to invasive BCC and shows extracellular matrix remodeling features.
2024-07-02 | GSE269601 | GEO
Project description:Hair follicles (HF) and BCCs can be regarded as ordered and disordered skin appendages respectively and may utilize similar molecular mechanisms of growth. We wanted to examine the similarities and differences in gene expression patterns between BCCs and HF to define common growth mechanisms and gene expression patterns that distinguish an ordered skin appendage from a disordered skin growth. Nodular BCCs (n= 8) and non-follicular skin epithelium (n=8) were obtained. Scalp hair follicle root sheath was micro dissected from between the sebaceous gland duct and the lower one third of the HF (n=7). Microarray analysis was performed using 21K cDNA arrays and selected genes were validated using qPCR and histochemistry staining. Two differentially expressed gene sets were identified by significance analysis of microarray (SAM) in BCC and HF verses skin epithelium respectively. Based on these two lists, we conducted multiple signaling pathway analyses. The results indicated that Notch, hedgehog, and WNT signaling pathways were involved in regulating formation of both HF and BCCs. However, Notch signaling, including tumor suppressor genes Notch 1, Notch 2, Jagged ligands (JAG 1, 2), notch signaling inhibitor NUMB, Lunatic Fringe (LFNG), Deltex proteins (DTX 1, 2) which serve as important signaling components downstream of Notch, and Notch target genes HES1 ,RBPSUHL, hairless protein and HES7, all showed selective differential activation in BCCs compared to HF. The components of the notch signaling pathway may be potential new targets in the development of new therapeutic approaches to BCCs. samples of human hair follicles (n=7) were collected from scalp biopsies of normal individuals undergoing cosmetic procedures while nodular BCCs (n=8) and normal skin (n=8) were obtained from patients undergoing surgical resection. Only patients that had not been treated with preoperative chemotherapy or other therapeutic approaches were selected. All samples were provided by the Department of Dermatology and Skin Science, University of British Columbia with approval from the University Clinical Research Ethics Board. Hair follicles were microdissected to remove the lower one third, including the hair bulb, leaving the root sheaths including the bulge region. Normal skin samples were microdissected to isolate skin epithelium from the dermal component. All nodular BCC samples and normal skin epithelium were taken from the facial area of donors. Collected samples were immediately stored in an RNA stabilization reagent (Qiagen Inc, Mississauga, ON). BCC morphological subtypes were described and clinically classified during surgery and clinical diagnoses were confirmed by formalin-fixed, paraffin embedded histological assessment of the tumors. Human Operon v.2.1 (21K) glass arrays were produced (based on human 70mers from Operon Biotechnologies Inc, Huntsville, AL) by the Microarray Facility of the Prostate Centre at Vancouver General Hospital, Vancouver, Canada [17, 18]. RNAs were amplified using the SenseAmp Plus kit (Genisphere Inc, Hatfield, PA). The calculated A 260/280 ratio was used to determine the appropriate amount of sense RNA for labeling. Total RNA from test samples and universal human reference RNA (Stratagene, Cedar Creek, TX) were differentially labeled with Cy5 and Cy3 respectively, with the 3DNA array detection 350 kit (Genisphere Inc, Hatfield, PA) and cohybridized to cDNA microarrays. Following overnight hybridization and washing, arrays were imaged using a ScanArray Express scanner (PerkinElmer, Boston, MA).
2010-06-20 | E-GEOD-12542 | biostudies-arrayexpress
Project description:BACKGROUND: Basal cell carcinoma (BCC) is the most common form of human cancer. Though the genetic mutation and subsequent aberrant signaling role of the Hedgehog pathway in BCC development is understood, little is known about the downstream genetic mechanisms underlying BCC growth. The characterization of molecular events would improve our understanding of carcinogenesis and may define new therapeutic intervention opportunities. OBJECTIVE: To identify differential gene expression associated with tumorigenesis promotion and to define common signaling pathways significant in BCC survival and growth. METHODS: Microarray analysis, using a 21K expanded sequence verified cDNA set was performed on tissues obtained from previously untreated patients undergoing Mohs surgical resection (8 superficial BCC, 8 nodular BCC, 7 morphea form, 8 normal skin). Significantly differentially expressed genes were identified by analysis of microarray results in various data sets and subsequently screened for signaling pathway involvement. Selected genes were validated using real-time PCR analysis using an expanded set of 31 BCC samples. RESULTS: The global gene expression profiles in BCCs and normal skin were distinguishable by unpaired T test. 2429 genes were at least 1.5 fold differentially expressed between BCC (all morphological types) and normal skin (p < 0.01). Multiple singaling pathways were activated, but the hedgehog, WNT, MAPK and calcium signal transduction pathways predominated. CONCLUSION: Our findings may have important implications for understanding the pathogenesis of BCC and suggest targeting of the WNT and MAPK pathways with therapeutic intervention. Keywords: disease state analysis
2006-12-15 | GSE6520 | GEO
Project description:In summary, we have validated differential expression of several miRs, namely two that are downregulated in all BCC subtypes compared to control skin (miR.383.5p, miR.145.5p), two that are downregulated in superficial BCC (miR.181c.5p, miR.181b.5p) relative to nodular and infiltrative BCC, and several that are upregulated in infiltrative BCC relative to superficial BCC (miR.22.5p, miR.18a.3p, miR.708.5p, miR.758.3p, miR.30c.5p), and two that are upregulated in infiltrative BCC relative to nodular BCC (miR.22.5p, miR.758.3p). To our knowledge, this study has investigated and validated the largest number of BCC tumors representing the different subtypes.
2024-01-01 | GSE245676 | GEO
Project description:Hair follicles (HF) and BCCs can be regarded as ordered and disordered skin appendages respectively and may utilize similar molecular mechanisms of growth. We wanted to examine the similarities and differences in gene expression patterns between BCCs and HF to define common growth mechanisms and gene expression patterns that distinguish an ordered skin appendage from a disordered skin growth. Nodular BCCs (n= 8) and non-follicular skin epithelium (n=8) were obtained. Scalp hair follicle root sheath was micro dissected from between the sebaceous gland duct and the lower one third of the HF (n=7). Microarray analysis was performed using 21K cDNA arrays and selected genes were validated using qPCR and histochemistry staining. Two differentially expressed gene sets were identified by significance analysis of microarray (SAM) in BCC and HF verses skin epithelium respectively. Based on these two lists, we conducted multiple signaling pathway analyses. The results indicated that Notch, hedgehog, and WNT signaling pathways were involved in regulating formation of both HF and BCCs. However, Notch signaling, including tumor suppressor genes Notch 1, Notch 2, Jagged ligands (JAG 1, 2), notch signaling inhibitor NUMB, Lunatic Fringe (LFNG), Deltex proteins (DTX 1, 2) which serve as important signaling components downstream of Notch, and Notch target genes HES1 ,RBPSUHL, hairless protein and HES7, all showed selective differential activation in BCCs compared to HF. The components of the notch signaling pathway may be potential new targets in the development of new therapeutic approaches to BCCs.
2008-09-02 | GSE12542 | GEO
Project description:Whole genome methylation profiling performed with Infinium MethylationEPIC BeadChips as well as RNA and smallRNA sequencing were performed in 5 sBCCs with the Illumina NextSeq500 next generation sequencing system.
2019-10-25 | GSE128784 | GEO