Browse
Submit Data
Databases
API
Help

Dataset Information

15 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Comprehensive mutational analysis of background mucosa in patients with Lugol-voiding lesions.

ABSTRACT: Somatic mutations including the background mucosa in patients with Lugol-voiding lesions (LVLs) are still not well known. The aim of this study was to evaluate the somatic mutations of the background mucosa in patients with LVLs (Squamous cell carcinoma (SCC), intraepithelial neoplasia (IN), and hyperplasia). Twenty-five patients with LVLs (9 with SCC, 6 with IN, and 10 with hyperplasia) were included. A targeted sequence was performed for LVLs and background mucosa using an esophageal cancer panel. Each mutation was checked whether it was oncogenic or not concerning OncoKB. In LVLs, TP53 was the most dominant mutation (80%). Furthermore, 72% of TP53 mutations was putative drivers. In background mucosa, NOTCH1 was the most dominant mutation (88%) and TP53 was the second most dominant mutation (48%). Furthermore, 73% of TP53 mutations and 8% of NOTCH1 mutations were putative drivers. Putative driver mutations of TP53 had significantly higher allele frequency (AF) in SCC than in IN and hyperplasia. Conversely, putative driver mutations of NOTCH1 did not have a significant accumulation of AF in the progression of carcinogenesis. Furthermore, in SCC, AF of TP53 mutations was significantly higher in LVLs than in background mucosa, but not in IN and hyperplasia. Regarding NOTCH1, a significant difference was not observed between LVLs and background mucosa in each group. The background mucosa in patients with LVLs already had putative driver mutations such as TP53 and NOTCH1. Of these two genes, TP53 mutation could be the main target gene of carcinogenesis in esophageal SCC. Clinical Trials registry: UMIN000034247.

SUBMITTER: Akizue N

PROVIDER: S-EPMC8178505 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Similar Datasets

Combination of Endoscopic Resection and Radiofrequency Ablation for the Treatment of Esophageal Squamous Cell Neoplasia With Multiple Lugol-Voiding Lesions.

Project description:BackgroundLocal recurrence of esophageal squamous cell neoplasia (ESCN) and metachronous ESCN was associated with severe background esophageal multiple Lugol-voiding lesions (LVLs) even though the primary early ESCNs were treated with endoscopic resection (ER). The aim of this study is to explore the feasibility and effectiveness of combination treatments of ER and radiofrequency ablation (RFA) in patients with early ESCNs with synchronous multiple LVLs.MethodsA total of 329 patients with early ESCNs and synchronous multiple LVLs received ER combined with RFA from September 2010 to September 2020. Clinical and pathological features and treatment outcomes were retrospectively reviewed using medical records. Factors associated with background esophageal multiple LVLs before combined treatment were analyzed.ResultsThe proportion of complete response (CR) was 96.7% after primary RFA, while 90.3% patients achieved CR for the last endoscopic examinations regardless if inside or outside the treatment area (TA). Degeneration of background esophageal multiple LVLs occurred in 70.2% of patients. The grade of background esophageal multiple LVLs before combined treatment was closely related to gender, smoking, and drinking. The incidence of metachronous ESCNs outside the TA of ER and local recurrence in the TA of ER was 3.9% and 1.2%, respectively.ConclusionsProphylactic RFA treatment of multiple LVLs together with ER treatment of the primary ESCNs may be effective in reducing the incidence of metachronous ESCNs and local recurrence through improving the background esophageal mucosa.

| S-EPMC8651547 | biostudies-literature

MutationalPatterns: comprehensive genome-wide analysis of mutational processes.

Project description:Base substitution catalogues represent historical records of mutational processes that have been active in a cell. Such processes can be distinguished by various characteristics, like mutation type, sequence context, transcriptional and replicative strand bias, genomic distribution and association with (epi)-genomic features.We have created MutationalPatterns, an R/Bioconductor package that allows researchers to characterize a broad range of patterns in base substitution catalogues to dissect the underlying molecular mechanisms. Furthermore, it offers an efficient method to quantify the contribution of known mutational signatures within single samples. This analysis can be used to determine whether certain DNA repair mechanisms are perturbed and to further characterize the processes underlying known mutational signatures.MutationalPatterns allows for easy characterization and visualization of mutational patterns. These analyses willsupport fundamental research into mutational mechanisms and may ultimately improve cancer diagnosis and treatment strategies. MutationalPatterns is freely available at http://bioconductor.org/packages/MutationalPatterns .

| S-EPMC5922316 | biostudies-other

Comprehensive Cohort Analysis of Mutational Spectrum in Early Onset Breast Cancer Patients.

Project description:Early onset breast cancer (EOBC), diagnosed at age ~40 or younger, is associated with a poorer prognosis and higher mortality rate compared to breast cancer diagnosed at age 50 or older. EOBC poses a serious threat to public health and requires in-depth investigation. We studied a cohort comprising 90 Taiwanese female patients, aiming to unravel the underlying mechanisms of EOBC etiopathogenesis. Sequence data generated by whole-exome sequencing (WES) and whole-genome sequencing (WGS) from white blood cell (WBC)-tumor pairs were analyzed to identify somatic missense mutations, copy number variations (CNVs) and germline missense mutations. Similar to regular breast cancer, the key somatic mutation-susceptibility genes of EOBC include TP53 (40% prevalence), PIK3CA (37%), GATA3 (17%) and KMT2C (17%), which are frequently reported in breast cancer; however, the structural protein-coding genes MUC17 (19%), FLG (16%) and NEBL (11%) show a significantly higher prevalence in EOBC. Furthermore, the top 2 genes harboring EOBC germline mutations, MUC16 (19%) and KRT18 (19%), encode structural proteins. Compared to conventional breast cancer, an unexpectedly higher number of EOBC susceptibility genes encode structural proteins. We suspect that mutations in structural proteins may increase physical permeability to environmental hormones and carcinogens and cause breast cancer to occur at a young age.

| S-EPMC7464007 | biostudies-literature

Atrophic and Metaplastic Progression in the Background Mucosa of Patients with Gastric Adenoma.

Project description:BackgroundIn patients with adenoma, assessing premalignant changes in the surrounding mucosa is important for surveillance. This study evaluated atrophic and metaplastic progression in the background mucosa of adenoma or early gastric cancer (EGC) cases.MethodsAmong 146 consecutive patients who underwent endoscopic resection for intestinal-type gastric neoplasia, the adenoma group included 56 patients with low-grade dysplasia and the ECG group included 90 patients with high-grade dysplasia or invasive carcinoma. For histology, 3 paired biopsies were obtained from the antrum, corpus lesser curvature (CLC), and corpus greater curvature (CGC). Serological atrophy was determined based on pepsinogen A (PGA), progastricsin (PGC), gastrin-17, and total ghrelin levels. Topographic progression of atrophy and/or metaplasia was staged using the operative link on gastritis assessment (OLGA) and operative link on gastric intestinal metaplasia assessment (OLGIM) systems.ResultsRates of moderate-to-marked histological atrophy/metaplasia in patients with adenoma were 52.7%/78.2% at the antrum (vs. 58.8%/76.4% in EGC group), 63.5%/75.0% at the CLC (vs. 60.2%/69.7% in EGC group), and 10.9%/17.9% at the CGC (vs. 5.6%/7.8% in EGC group). Serological atrophy indicated by PGA and PGC occurred in 23.2% and 15.6% of cases in the adenoma and ECG groups, respectively (p = 0.25). Mean serum gastrin-17 concentrations of the adenoma group and EGC group were 10.4 and 9.0 pmol/L, respectively (p = 0.54). Mean serum total ghrelin levels were 216.6 and 209.5 pg/mL, respectively (p = 0.71). Additionally, between group rates of stage III-IV OLGA and OLGIM were similar (25.9% vs. 25.0%, p = 0.90; 41.8% vs. 44.9%, p = 0.71, respectively).ConclusionsAtrophic and metaplastic progression is extensive and severe in gastric adenoma patients. A surveillance strategy for metachronous tumors should be applied similarly for patients with adenoma or EGC.

| S-EPMC5225017 | biostudies-literature

Comprehensive analysis identifying aberrant DNA methylation in rectal mucosa from ulcerative colitis patients with neoplasia.

Project description:BackgroundThere are no biomarkers to facilitate the identification of patients with ulcerative colitis (UC) who are at high risk for developing colorectal cancer (CRC). In our current study, we used rectal tissues from UC patients to identify aberrant DNA methylations and evaluated whether they could be used to identify UC patients with coexisting colorectal neoplasia.ResultsUsing a training set, we identified 484 differentially methylated regions (DMRs) with absolute delta beta-values > 0.1 in rectal mucosa by using the ChAMP algorithm. Next, pathway enrichment analysis was performed using 484 DMRs to select coordinately methylated DMRs, resulting in the selection of 187 aberrant DMRs in rectal tissues from UC-CRC. Then, the Elastic Net classification algorithm was performed to narrow down optimal aberrant DMRs, and we finally selected 11 DMRs as biomarkers for identification of UC-CRC patients. The 11 chosen DMRs could discriminate UC patients with or without CRC in a training set (area under the curve, 0.96) and the validation set (area under the curve, 0.81).ConclusionsIn conclusion, we identified 11 DMRs that could identify UC patients with CRC complications. Prospective studies should further confirm the validity of these biomarkers.MethodsWe performed genome-wide DNA methylation profiles in rectal mucosal tissues (n = 48) from 24 UC-CRC and 24 UC patients in a training set. Next, we performed comprehensive DNA methylation analysis using rectal mucosal tissues (n = 16) from 8 UC-CRC and 8 UC patients for validation.

| S-EPMC6145694 | biostudies-literature

Comprehensive mutational analysis of primary and relapse acute promyelocytic leukemia

Project description:Acute promyelocytic leukemia (APL) is a subtype of myeloid leukemia characterized by differentiation block at the promyelocyte stage. Besides the presence of chromosomal rearrangement t(15;17) leading to formation of PML-RARA fusion, other genetic alterations have also been implicated in APL. Here, we performed comprehensive mutational analysis of primary and relapse APL to identify somatic alterations which cooperate with PML-RARA in the pathogenesis of APL. We explored the mutational landscape using whole-exome (n=12) and subsequent targeted sequencing of 398 genes in 153 primary and 69 relapse APL. Both primary and relapse APL harbored an average of eight non-silent somatic mutations per exome. We observed recurrent alterations of FLT3, WT1, NRAS and KRAS in the newly diagnosed APL, while mutations in other genes commonly mutated in myeloid leukemia were rarely detected. The molecular signature of APL relapse was characterized by emergence of frequent mutations in PML and RARA genes. Our sequencing data also demonstrates incidence of loss-of-function mutations in previously unidentified genes, ARID1B and ARID1A, both of which encode for key components of the SWI/SNF complex. We show that knockdown of ARID1B in APL cell line, NB4, results in large scale activation of gene expression and reduced in vitro differentiation potential. Studying the effects of silensing ARID1B gene in NB4 cell lines

2016-02-17 | E-GEOD-77946 | biostudies-arrayexpress

Comprehensive mutational analysis of primary and relapse acute promyelocytic leukemia.

Project description:Acute promyelocytic leukemia (APL) is a subtype of myeloid leukemia characterized by differentiation block at the promyelocyte stage. Besides the presence of chromosomal rearrangement t(15;17), leading to the formation of PML-RARA (promyelocytic leukemia-retinoic acid receptor alpha) fusion, other genetic alterations have also been implicated in APL. Here, we performed comprehensive mutational analysis of primary and relapse APL to identify somatic alterations, which cooperate with PML-RARA in the pathogenesis of APL. We explored the mutational landscape using whole-exome (n=12) and subsequent targeted sequencing of 398 genes in 153 primary and 69 relapse APL. Both primary and relapse APL harbored an average of eight non-silent somatic mutations per exome. We observed recurrent alterations of FLT3, WT1, NRAS and KRAS in the newly diagnosed APL, whereas mutations in other genes commonly mutated in myeloid leukemia were rarely detected. The molecular signature of APL relapse was characterized by emergence of frequent mutations in PML and RARA genes. Our sequencing data also demonstrates incidence of loss-of-function mutations in previously unidentified genes, ARID1B and ARID1A, both of which encode for key components of the SWI/SNF complex. We show that knockdown of ARID1B in APL cell line, NB4, results in large-scale activation of gene expression and reduced in vitro differentiation potential.

| S-EPMC4972641 | biostudies-literature

Mutational analysis of patients with neurofibromatosis 2.

Project description:Neurofibromatosis 2 (NF2) is a genetic disorder characterized by the development of multiple nervous-system tumors in young adulthood. The NF2 gene has recently been isolated and found to encode a new member of the protein 4.1 family of cytoskeletal associated proteins, which we have named merlin. To define the molecular basis of NF2 in affected individuals, we have used SSCP analysis to scan the exons of the NF2 gene from 33 unrelated patients with NF2. Twenty unique SSCP variants were seen in 21 patients; 10 of these individuals were known to be the only affected person in their kindred, while 7 had at least one other known affected relative. In all cases in which family members were available, the SSCP variant segregated with the disease; comparison of sporadic cases with their parents confirmed the de novo variants. DNA sequence analysis revealed that 19 of the 20 variants observed are predicted to lead to a truncated protein due to frameshift, creation of a stop codon, or interference with normal RNA splicing. A single patient carried a 3-bp deletion removing a phenylalanine residue. We conclude that the majority of NF2 patients carry an inactivating mutation of the NF2 gene and that neutral polymorphism in the gene is rare.

| S-EPMC1918355 | biostudies-other

Project description:Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the virus responsible for coronavirus disease 2019 (COVID-19), which manifests as a flu-like respiratory infection affecting multiple organ systems, including the gastrointestinal system, central nervous system, cardiovascular system, skin, and mucosa. In this review, we investigated the literature on specific manifestations of COVID-19 in the oral mucosa. An online literature search in PubMed, Scopus, Google Scholar, and Medline was conducted to retrieve relevant studies on confirmed COVID-19 patients with oral mucosa findings published between December 31, 2019, and April 07, 2021. After an independent review by two authors, 39 articles considering 59 laboratory-confirmed cases of SARS-CoV-2 infection were included in the final analysis. The most common finding, reported in 29 patients (43.9%), was Kawasaki-like syndrome. In addition, oral ulcers including aphthous, hemorrhagic, and necrotic ulcers were reported in 24 patients (36.3%). Other lesions reported included pustules, macules, bullae, maculopapular enanthema, and erythema multiforme-like lesions. Concomitant skin lesions were present in 60.6% of patients. Fever was reported in 86.2% of patients. Forty-eight patients (76.1%) were hospitalized. Loss of taste and smell was present in 30.8% of the patients. A comprehensive understanding of the dermatologic manifestations of COVID-19 can improve and facilitate patient management and referrals.

| S-EPMC8652904 | biostudies-literature

Exploring background mutational processes to decipher cancer genetic heterogeneity.

Project description:Much remains unknown about the progression and heterogeneity of mutational processes in different cancers and their diagnostic and clinical potential. A growing body of evidence supports mutation rate dependence on the local DNA sequence context for various types of mutations. We propose several tools for the analysis of cancer context-dependent mutations, which are implemented in an online computational framework MutaGene. The framework explores DNA context-dependent mutational patterns and underlying somatic cancer mutagenesis, analyzes mutational profiles of cancer samples, identifies the combinations of underlying mutagenic processes including those related to infidelity of DNA replication and repair machinery, and various other endogenous and exogenous mutagenic factors. As a result, the combination of mutagenic processes can be identified in any query sample with subsequent comparison to mutational profiles derived from malignant and benign samples. In addition, mutagen or cancer-specific mutational background models are applied to calculate expected DNA and protein site mutability to decouple relative contributions of mutagenesis and selection in carcinogenesis, thus elucidating the site-specific driving events in cancer. MutaGene is freely available at https://www.ncbi.nlm.nih.gov/projects/mutagene/.

| S-EPMC5793731 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data