The genetic architecture of breast papillary lesions as a predictor of progression to carcinoma
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ABSTRACT:
PROVIDER: PRJNA542641 | ENA |
REPOSITORIES: ENA
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Project description:We analysed a cohort of breast papillary lesions cases with (n=4) or without (n=7) co-existed cancer for genome-wide copy number and loss of heterozygosity using Affymetrix OncoScan® MIP arrays. Cases included pure papilloma (withoout cancer) (n=7), papilloma cases synchronous with cancer (n=4). We have analysed copy number calling from these samples including carcinoma components of synchronous cases in order to understand the precursor relationship as well any biomarker for progression from papillary lesions to carcinoma.
2020-01-29 | GSE131087 | GEO
Project description:Intraductal papillomas (IDP) are challenging breast findings because of their variable risk of progression to malignancy. The molecular events driving IDP development and genomic features of malignant progression are poorly understood. In this study, genome-wide CNA and/or targeted mutation analysis was performed on 44 cases of IDP, of which 20 cases had coexisting ductal carcinoma in situ (DCIS), papillary DCIS or invasive ductal carcinoma (IDC). CNA were rare in pure IDP, but 69% carried an activating PIK3CA mutation. Among the synchronous IDP cases, 55% (11/20) were clonally related to the synchronous DCIS and/or IDC, only one of which had papillary histology. In contrast to pure IDP, PIK3CA mutations were absent from clonal cases. CNAs in any of chromosomes 1, 16 or 11 were significantly enriched in clonal IDP lesions compared to pure and non-clonal IDP. The observation that 55% of IDP are clonal to DCIS/IDC indicates that IDP can be a direct precursor for breast carcinoma, not limited to the papillary type. The absence of PIK3CA mutations and presence of CNAs in IDP could be used clinically to identify patients at high risk of progression to carcinoma.
| S-EPMC7067788 | biostudies-literature
Project description:Individuals who present with premalignant endobronchial lesions are considered at high risk of lung cancer. Nonetheless, premalignant lesions behave erratically and only a minority progresses towards lung cancer. Therefore, biomarkers need to be discovered that can aid in assessing an individual’s risk for subsequent cancer to better tailor treatment choices and avoid unnecessary follow-up procedures. We recently proposed a classifier of DNA copy number alterations (CNAs) at 3p26.3-p11.1, 3q26.2-29, and 6p25.3-24.3 as risk predictor for endobronchial cancer. The current study was set out to validate the classifier among an independent series of premalignant endobronchial lesions with various histological grades. A series of 36 endobronchial premalignant lesions (8 squamous metaplasia, and 28 various grades of dysplasia) identified during autofluorescence bronchoscopy of 12 case subjects who had carcinoma in situ or carcinoma (≥CIS) during follow-up bronchoscopy at the initial site and 24 control subjects who remained cancer-free, was subjected to array Comparative Genomic Hybridization (arrayCGH). DNA copy number profiles were related to lesion outcome. Prediction accuracy of the previously defined molecular classifier to predict endobronchial cancer in this series was determined. Unsupervised hierarchical clustering analysis revealed a significant association between cluster assignment and lesion outcome (p< 0.001), independent of histological grade, with quiescent profiles in controls (24/24) and aberrant profiles in the majority of cases (9/12). Our pre-defined classifier demonstrated 92% accuracy for predicting cancer outcome in the current sample series. Our validated classifier holds great promise for stratification of patients with premalignant endobronchial lesions for risk of subsequent cancer. Fresh frozen specimens of 36 premalignant endobronchial biopsies. Test samples were compared to an external pool of normal male/female reference DNA.
2013-12-03 | E-GEOD-45287 | biostudies-arrayexpress
Project description:Individuals who present with premalignant endobronchial lesions are considered at high risk of lung cancer. Nonetheless, premalignant lesions behave erratically and only a minority progresses towards lung cancer. Therefore, biomarkers need to be discovered that can aid in assessing an individual’s risk for subsequent cancer to better tailor treatment choices and avoid unnecessary follow-up procedures. We recently proposed a classifier of DNA copy number alterations (CNAs) at 3p26.3-p11.1, 3q26.2-29, and 6p25.3-24.3 as risk predictor for endobronchial cancer. The current study was set out to validate the classifier among an independent series of premalignant endobronchial lesions with various histological grades. A series of 36 endobronchial premalignant lesions (8 squamous metaplasia, and 28 various grades of dysplasia) identified during autofluorescence bronchoscopy of 12 case subjects who had carcinoma in situ or carcinoma (≥CIS) during follow-up bronchoscopy at the initial site and 24 control subjects who remained cancer-free, was subjected to array Comparative Genomic Hybridization (arrayCGH). DNA copy number profiles were related to lesion outcome. Prediction accuracy of the previously defined molecular classifier to predict endobronchial cancer in this series was determined. Unsupervised hierarchical clustering analysis revealed a significant association between cluster assignment and lesion outcome (p< 0.001), independent of histological grade, with quiescent profiles in controls (24/24) and aberrant profiles in the majority of cases (9/12). Our pre-defined classifier demonstrated 92% accuracy for predicting cancer outcome in the current sample series. Our validated classifier holds great promise for stratification of patients with premalignant endobronchial lesions for risk of subsequent cancer.
2013-12-03 | GSE45287 | GEO
Project description:The dysregulation of circular RNAs (circRNAs) has been implicated in the development and progression of papillary thyroid cancer (PTC). In this study, we analyzed the dysregulated circRNA profile using PTC tissues and matched adjacent normal tissues by RNA-seq.
2023-07-27 | GSE237841 | GEO
Project description:Gene expression data of fibroepithelial lesions of the breast
2015-01-01 | GSE55224 | GEO
Project description:Experiment a) Establishment of expression profiles in conventional papillary thyroid carcinomas (PTCs) with a BRAF mutation vs. PTCs without a BRAF mutation and using normal thyroid (TN) specimens as reference. Experiment b) Establishment of expression profiles in follicular adenomas (FAs) of the thyroid and follicular variant of papillary thyroid carcinomas (FVPTCs). We extracted DNA from specimens and performed mutational analysis in malignant lesions and extracted RNA that was processed and hybridized to Affymetrix microarrays.
2015-02-16 | E-GEOD-54958 | biostudies-arrayexpress
Project description:Anaplastic thyroid carcinoma (ATC) has among the worst prognosis of any solid malignancy. The low incidence of the disease has in part precluded systematic clinical trials and tissue collection, and there has been little progress in developing effective therapies. BRAF and TP53 mutations co-occur in a high proportion of ATC, particularly those associated with a precursor papillary thyroid carcinoma (PTC). In order to develop an adult-onset model of BRAF-mutant anaplastic thyroid carcinoma, we generated a novel thyroid-specific CreER transgenic mouse. We utilize a Cre-regulated BrafV600E mouse and a conditional Trp53 allelic series to demonstrate that p53 constrains progression from papillary to anaplastic thyroid carcinoma. Gene expression and immunohistochemical analyses of murine tumors identified the cardinal features of human ATC including loss of differentiation, local invasion, distant metastasis and rapid lethality. We employed small animal ultrasound imaging to monitor autochthonous tumors, and show that treatment with the selective BRAF inhibitor PLX4720 improved survival, but did not lead to tumor regression or suppress signaling through the MAPK pathway. Combination of PLX4720 and the MEK inhibitor PD0325901 more completely suppressed MAPK pathway activation in mouse and human ATC cell lines, and improved the structural response and survival of ATC-bearing animals. This model expands the limited repertoire of autochthonous models of clinically aggressive thyroid cancer, and these data suggest that small molecule MAPK pathway inhibitors hold clinical promise in the treatment of advanced thyroid carcinoma. Total RNA from five murine papillary thyroid carcinoma (PTC) tumors and five murine anaplastic thyroid carcinoma (ATC) tumors was analyzed.
2014-04-02 | E-GEOD-55933 | biostudies-arrayexpress
Project description:Purpose: The aim of this study is to investigate mechanisms driving tumor-promoting mechanisms in cholangiocarcinoma while focusing on transitions from normal cholangiocytes to precancer lesions and from precancer lesion to invasive carcinoma. An original mouse model of intrahepatic cholangiocarcinoma was developed, based on induction of a KrasG12D mutation in cholangiocytes combined with chronic inflammation. RNA-Seq analyses compare the transcriptome of ductular proliferations, intraductal papillary neoplasm of the bile duct and intrahepatic cholangiocarcinoma. A gene cascade involving EGF, KrasG12D, Sox17 and Tns4 was identified to promote tumor progression.
2021-03-29 | GSE141511 | GEO
Project description:Bronchial premalignant lesions have distinct molecular subtypes associated with future histologic progression
| PRJNA431899 | ENA