Project description:Background & aim: Flat adenomas form a specific phenotype of colorectal adenomas that has been associated with more severe molecular changes and consequently a more aggressive clinical behavior compared to their polypoid counterparts. In the present study we set out to compare one of the molecular changes most explicitly associated with adenoma to carcinoma progression, i.e. chromosomal instability, between flat and polypoid colorectal adenomas. Methods: Consecutive series of 83 flat and 35 polypoid adenomas were analyzed for DNA copy number changes using a high resolution arrayCGH platform as well as for mutations in the adenomatous polyposis coli (APC) gene. Gene ontology on the genes located on the significantly different regions was performed. Results: Overall, flat adenomas show similar DNA copy number changes as polypoid adenomas. Patterns of DNA copy number changes differed between the two phenotypes with significantly more frequently loss of 5q14.3 and 5q15-q23.3 in flat adenomas, while loss of 1p36.32-p35.3, 10q25.2-q25.3, 17p12 and chromosome 18 were more frequent in polypoid adenomas. The 5q15-q23.3 region harbors the APC locus, therefore mutation status of APC was investigated, showing significantly less mutations in flat adenomas. Pathway analysis and datamining linked the 5q region to inflammation. Conclusion: These results provide evidence that flat and polypoid adenomas have partly overlapping DNA copy number changes, while alterations more specific to flat adenomas have associations with inflammation. Loss of 5q has been associated with aggressive behavior and this could serve as an explanation for a more aggressive clinical behavior of flat lesions.
Project description:The vestibular sensory epithelium may degenerate into a layer of flat cells, known as flat epithelium, after a severe lesion, but the pathogenesis of vestibular flat epithelium remains unclear. We used microarrays to detail the global programme of gene expression in normal utricle and vestibular flat epithelium and identified whether epithelial-mesenchymal transition participite in this process
Project description:Background & aim: Flat adenomas form a specific phenotype of colorectal adenomas that has been associated with more severe molecular changes and consequently a more aggressive clinical behavior compared to their polypoid counterparts. In the present study we set out to compare one of the molecular changes most explicitly associated with adenoma to carcinoma progression, i.e. chromosomal instability, between flat and polypoid colorectal adenomas. Methods: Consecutive series of 83 flat and 35 polypoid adenomas were analyzed for DNA copy number changes using a high resolution arrayCGH platform as well as for mutations in the adenomatous polyposis coli (APC) gene. Gene ontology on the genes located on the significantly different regions was performed. Results: Overall, flat adenomas show similar DNA copy number changes as polypoid adenomas. Patterns of DNA copy number changes differed between the two phenotypes with significantly more frequently loss of 5q14.3 and 5q15-q23.3 in flat adenomas, while loss of 1p36.32-p35.3, 10q25.2-q25.3, 17p12 and chromosome 18 were more frequent in polypoid adenomas. The 5q15-q23.3 region harbors the APC locus, therefore mutation status of APC was investigated, showing significantly less mutations in flat adenomas. Pathway analysis and datamining linked the 5q region to inflammation. Conclusion: These results provide evidence that flat and polypoid adenomas have partly overlapping DNA copy number changes, while alterations more specific to flat adenomas have associations with inflammation. Loss of 5q has been associated with aggressive behavior and this could serve as an explanation for a more aggressive clinical behavior of flat lesions. FFPE colorectal tissue samples of 35 polypoid adenomas and 83 flat adenomas. Test samples were compared to an external pool of normal male/female reference DNA.
Project description:The developing vertebrate growth plates in long bones have three morphologically distinct layers of chondrocytes: Round Cell layer, Flat Cell layer, and Hypertrophic Cell layer. Round chondrocytes differentiate into flat chondrocytes, and then flat chondrocytes differentiate into hypertrophic chondrocytes. To investigate the genetic programs underlying the chondrocyte differentiation, we obtained total RNA from the microdissected cryosections from each layer and then performed microarray analysis.
Project description:Low grade flat ductal intraepithelial neoplasia (DIN1a, flat epithelial atypia) is one of the earliest morphologically recognizable neoplastic lesions of the breast. Frequently, it occurs in association with lobular intraepithelial neoplasia (LIN). The aim of this study was to elucidate chromosomal aberrations in these early neoplastic breast lesions using array comparative genomic hybridization (CGH) analysis. Laser capture microdissection of 12 archival formalin-fixed, paraffin-embedded specimens harbouring both foci of DIN1a as well as LIN was performed. All analyzed cases of DIN1a and LIN showed chromosomal gains and losses. The aberration encountered most often was loss on 16q in 7 DIN1a (70%) and 10 LIN (91%) cases. Regarding changes in chromosome 1, four DIN1a (40%) and 7 LIN (64%) cases showed a gain on 1q. The results of our study show concurrent chromosomal aberrations of 1q gains and 16q losses in several cases with coexisting LIN and low grade flat DIN. These aberrations are known to be common in low grade invasive ductal carcinomas as well as more advanced (conventional) types of low grade DIN (low grade ductal carcinoma in-situ). Our results raise the possibility of similar molecular-genetic pathways in most of the cases with coexisting LIN and low grade flat DIN.
Project description:Patients with ulcerative colitis (UC) are at increased risk of colorectal cancer (CRC). Colitis-associated dysplasia (flat or polypoid) continues to be a reliable marker for CRC in these patients. However, flat lesions are often missed during endoscopy and can rapidly progress to high-grade dysplasia or cancer. microRNAs (miRs), small non-coding RNAs, have emerged as a valuable diagnostic biomarker of human cancer due to their ease of detection and stability. The goal of this study was to identify a miR signature that can serve as a reliable biomarker for the early detection of colitis-associated dysplasia in patients with long-standing colitis.
Project description:gnp3_tri33-arabidoseed. Embryo seed development. WP3: Biodiversity of seed traits: state-of-the-art. Analysis of the expression of small RNAs precursors in the seed development of Arabidopsis thaliana.
Project description:RNA-seq analysis revealed that genes associated with lacrimal gland development, such as BARX2, SIX1, SIX2, SOX9, and KRT15, were upregulated in domed colonies compared to flat colonies. In flat colonies, mucosal epithelial keratin, KRT13 and the corneal epithelial progenitor cell markers, CDH2 and NGFR were up-regulated, along with YAP1 and its downstream genes, CTGF and CYR61, which are involved in epithelial development.