Analysis of donor pancreata defines the transcriptomic signature and microenvironment of early neoplastic pancreatic lesions.
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PROVIDER: PRJNA946019 | ENA |
REPOSITORIES: ENA
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Project description:The adult healthy human pancreas has been poorly studied given lack of indication to obtain tissue from the pancreas in the absence of disease and rapid postmortem degradation. We obtained pancreata from brain dead donors thus avoiding any warm ischemia time. We found that neoplastic lesions occur frequently in healthy organs, in donors as young as in their 3rd decade of life. Using the 10X Genomics Platform, we performed single cell RNA sequencing on 6 donor pancreata, 5 of which we separately sequenced tissue from the pancreas head and tail, for a total of 11 sequencing runs. This is a robust single-cell dataset of healthy, nonpathologic pancreas tissue and includes acinar, ductal, and non-epithelial cells (myeloid cells, fibroblasts, endothelial cells, lymphocytes). We compared this dataset of normal pancreata to single cell sequencing of tumor samples previously published in Steele, et al, Nature Cancer 2020, (raw fastq in dbGap phs002071) realigned to GRCh38 reference genome (CellRanger 6.0). This GEO series contains the raw and filtered feature matrices for the donor pancreata as well as the realigned tumor samples. Supplementary files contain the aggregate feature matrices and the metadata of the donor pancreata samples and the tumor samples.
2023-05-01 | GSE229413 | GEO
Project description:Analysis of donor pancreata defines the transcriptomic signature and microenvironment of early neoplastic lesions.
| PRJNA954383 | ENA
Project description:Analysis of donor pancreata defines the transcriptomic signature and microenvironment of early neoplastic pancreatic lesions.
| PRJNA946020 | ENA
Project description:Analysis of donor pancreata defines the transcriptomic signature and microenvironment of early pre-neoplastic pancreatic lesions
| PRJNA941855 | ENA
Project description:The adult healthy human pancreas has been poorly studied given lack of indication to obtain tissue from the pancreas in the absence of disease and rapid postmortem degradation. We obtained pancreata from brain dead donors thus avoiding any warm ischemia time. The 30 donors were diverse in age and race and had no known pancreas disease. Histopathological analysis of the samples revealed PanIN lesions in most individuals irrespective of age. Using a combination of multiplex immunohistochemistry, single cell RNA sequencing, and spatial transcriptomics, we provide the first ever characterization of the unique microenvironment of the adult human pancreas and of sporadic PanIN lesions. We compared healthy pancreata to pancreatic cancer and peritumoral tissue and observed distinct transcriptomic signatures in fibroblasts, and, to a lesser extent, macrophages. PanIN epithelial cells from healthy pancreata were remarkably transcriptionally similar to cancer cells, suggesting that neoplastic pathways are initiated early in tumorigenesis.
2023-03-08 | GSE226829 | GEO
Project description:The adult healthy human pancreas has been poorly studied given the lack of indication to obtain tissue from the pancreas in the absence of disease and rapid postmortem degradation. We obtained pancreata from brain dead donors, thus avoiding any warm ischemia time. The 30 donors were diverse in age and race and had no known pancreas disease. Histopathologic analysis of the samples revealed pancreatic intraepithelial neoplasia (PanIN) lesions in most individuals irrespective of age. Using a combination of multiplex IHC, single-cell RNA sequencing, and spatial transcriptomics, we provide the first-ever characterization of the unique microenvironment of the adult human pancreas and of sporadic PanIN lesions. We compared healthy pancreata to pancreatic cancer and peritumoral tissue and observed distinct transcriptomic signatures in fibroblasts and, to a lesser extent, macrophages. PanIN epithelial cells from healthy pancreata were remarkably transcriptionally similar to cancer cells, suggesting that neoplastic pathways are initiated early in tumorigenesis.SignificancePrecursor lesions to pancreatic cancer are poorly characterized. We analyzed donor pancreata and discovered that precursor lesions are detected at a much higher rate than the incidence of pancreatic cancer, setting the stage for efforts to elucidate the microenvironmental and cell-intrinsic factors that restrain or, conversely, promote malignant progression. See related commentary by Hoffman and Dougan, p. 1288. This article is highlighted in the In This Issue feature, p. 1275.
| S-EPMC10236159 | biostudies-literature
Project description:The identification of genomic alterations occurring in neoplastic lesions provides insight into both lesion occurrence and disease progression. In this study we used microarray comparative genomic hybridization (CGH) to investigate genetic changes in atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS), as the presence of these lobular neoplastic lesions is an indicator of risk in the development of invasive breast cancer. DNA was extracted from microdissected archival breast tissue containing ALH or LCIS, lacking adjacent invasive carcinoma, and subjected to whole-genome tiling path microarray-CGH using the submegabase resolution tiling set (SMRTr)-array platform. Twelve ALH and 13 LCIS lesions were examined. Copy number alterations were identified using statistical criteria and validated with Real-Time PCR and fluorescence in situ hybridization. From statistical analysis, a greater number of alterations were observed in ALH compared to LCIS. Alterations common to ALH include gain at 2p11.2 and loss at 7p11.2-p11.1 and 22q11.1. Alterations common to LCIS include gain at 20q13.13 and loss at 19q13.2-q13.31. In both ALH and LCIS, we observed loss of 16q21-q23.1, an altered region previously identified in lobular neoplasia and invasive carcinoma. The validation of select alterations reinforces the genomic signature. This study represents the first whole-genome investigation of lobular neoplastic breast lesions using clinical archival specimens. The identified genomic signature includes copy number alterations not previously identified for lobular neoplasia. This genomic signature, common to ALH and LCIS, suggests a role for the acquisition of novel genomic alterations in the aberrant cellular proliferation that defines lobular neoplasia. Keywords: comparative genomic hybridization, high resolution analysis of atypical lobular hyperplasia (ALH) and lobular carcinoma in situ (LCIS) human archival breast lesions by whole genome tiling path array CGH
2006-08-01 | GSE4591 | GEO
Project description:Interventions: From November 2010 to August 2012 Following the detection of colorectal lesions in WL observation, the lesions were diagnosed for neoplastic or non-neoplastic.
In autofluorescence mode, color-tone sampling is performed on the area that had no halation or no bleeding points which might hamper analysis by the other endoscopist who did not know details of the lesion. Surrounding normal colonic mucosa was also analyzed for its color-tone in order to compare both G/R ratios. Lesions with G/R of < 1.01 are judged to be neoplastic and that with G/R of > 1.01 are considered to be non-neoplastic. Consecutively, all lesions analyzed in the present study are endoscopically removed or biopsied and the specimens are submitted to pathologic evaluation. Finally, pre-removal diagnoses and final pathological diagnoses are compared to each other in order to calculate the diagnostic yield of G/R ratio in the differential diagnosis of colorectal neoplastic lesions from non-neoplastic lesions. Pathologic diagnosis Histopathologic examination of the endoscopically or surgically resected specimen was performed on hematoxylin and eosin-stained sections, with reference to Japanese classification of colorectal carcinoma4. Lesions were classified into 2 categories based on the final pathological diagnoses, neoplastic lesions and non-neoplastic lesions. Neoplastic lesions included 5 pathological types, submucosal invasive cancer, intramucosal cancer, tubular or villous adenoma, traditional serrated adenoma (TSA) and sessile serrated adenoma (SSA). Non-neoplastic lesion included only hyperplastic lesion.
Primary outcome(s): Diagnostic yields of the cut-off value for AF index in the differential diagnosis between colorectal neoplastic and non-neoplastic lesions
Study Design: Parallel Non-randomized
| 2622947 | ecrin-mdr-crc
Project description:Oncogene-induced senescence in early mPanIN lesions depends on intact RelA function in vivo. We investigated the difference in gene expression between KrasG12D pancreata with and without deletion of RelA. Pancreata from 7 day old mice were prepared, RNA was isolated and Affymetrix microarray expression analysis was performed.
2017-06-01 | E-MTAB-1036 | biostudies-arrayexpress
Project description:This study used Illumina strand-specific, paired-end RNA-sequencing to examine gene expression differences between normal and neoplastic mouse pancreatic ductal cells grown as three-dimensional, organoid cultures. The study analyzed 19 independently derived organoid lines. These 19 lines included 7 biological replicate "mN," or mouse normal, organoid lines, derived from the pancreatic ductal cells of wild-type C57Bl/6J or C57Bl/6N mice. In addition, the study analyzed 6 biological replicate "mP," or mouse PanIN, organoid lines, derived from PanIN-containing mouse pancreata from the KrasLSL-G12D; Pdx1-Cre mouse model. (The presence of PanIN in the pancreata from which these organoid lines were derived was confirmed by examining histological sections from the same pancreata). The final 6 lines examined in this study were biological replicate "mT," or mouse tumor, organoid lines, derived from mouse pancreata containing pancreatic ductal adenocarcinoma (PDAC) from the KrasLSL-G12D; Trp53LSL-R162H; Pdx1-Cre mouse model. We genes differentially expressed in the PanIN- or tumor-derived mouse organoid lines, relative to the mouse normal organoids, that may reflect expression changes required for pancreatic tumorigenesis.
2014-12-30 | GSE63348 | GEO