Comprehensive analyses of DNA methylation of the TIMP3 promoter in placentas from early-onset and late-onset preeclampsia

Abstract The present study was performed to clarify the significance of DNA methylation alterations during endometrial carcinogenesis. Genome-wide DNA methylation analysis and targeted sequencing of tumor-related genes were performed using the Infinium MethylationEPIC BeadChip and the Ion AmpliSeq Cancer Hotspot Panel v2, respectively, for 31 samples of normal control endometrial tissue from patients without endometrial cancer and 81 samples of endometrial cancer tissue. Principal component analysis revealed that tumor samples had a DNA methylation profile distinct from that of control samples. Gene Ontology enrichment analysis revealed significant differences of DNA methylation at 1034 CpG sites between early-onset endometrioid endometrial cancer (EE) tissue (patients aged ≤40 years) and late-onset endometrioid endometrial cancer (LE) tissue, which were accumulated among ‘transcriptional factors’. Mutations of the CTNNB1 gene or DNA methylation alterations of genes participating in Wnt signaling were frequent in EEs, whereas genetic and epigenetic alterations of fibroblast growth factor signaling genes were observed in LEs. Unsupervised hierarchical clustering grouped EE samples in Cluster EA (n = 22) and samples in Cluster EB (n = 12). Clinicopathologically less aggressive tumors tended to be accumulated in Cluster EB, and DNA methylation levels of 18 genes including HOXA9, HOXD10 and SOX11 were associated with differences in such aggressiveness between the two clusters. We identified 11 marker CpG sites that discriminated EB samples from EA samples with 100% sensitivity and specificity. These data indicate that genetically and epigenetically different pathways may participate in the development of EEs and LEs, and that DNA methylation profiling may help predict tumors that are less aggressive and amenable to fertility preservation treatment.

Download Full-text

DNA Methylation Signatures and the Contribution of Age-Associated Methylomic Drift to Carcinogenesis in Early-Onset Colorectal Cancer

Cancers ◽

10.3390/cancers13112589 ◽

2021 ◽

Vol 13 (11) ◽

pp. 2589

Author(s):

Jihoon E. Joo ◽

Mark Clendenning ◽

Ee Ming Wong ◽

Christophe Rosty ◽

Khalid Mahmood ◽

...

Keyword(s):

Colorectal Cancer ◽

Dna Methylation ◽

Early Onset ◽

Late Onset ◽

Normal Mucosa ◽

Accelerated Ageing ◽

Normal Colonic Mucosa ◽

Age Related ◽

Differentially Methylated Genes ◽

Early Onset Colorectal Cancer

We investigated aberrant DNA methylation (DNAm) changes and the contribution of ageing-associated methylomic drift and age acceleration to early-onset colorectal cancer (EOCRC) carcinogenesis. Genome-wide DNAm profiling using the Infinium HM450K on 97 EOCRC tumour and 54 normal colonic mucosa samples was compared with: (1) intermediate-onset CRC (IOCRC; diagnosed between 50–70 years; 343 tumour and 35 normal); and (2) late-onset CRC (LOCRC; >70 years; 318 tumour and 40 normal). CpGs associated with age-related methylation drift were identified using a public dataset of 231 normal mucosa samples from people without CRC. DNAm-age was estimated using epiTOC2. Common to all three age-of-onset groups, 88,385 (20% of all CpGs) CpGs were differentially methylated between tumour and normal mucosa. We identified 234 differentially methylated genes that were unique to the EOCRC group; 13 of these DMRs/genes were replicated in EOCRC compared with LOCRCs from TCGA. In normal mucosa from people without CRC, we identified 28,154 CpGs that undergo ageing-related DNAm drift, and of those, 65% were aberrantly methylated in EOCRC tumours. Based on the mitotic-based DNAm clock epiTOC2, we identified age acceleration in normal mucosa of people with EOCRC compared with normal mucosa from the IOCRC, LOCRC groups (p = 3.7 × 10−16) and young people without CRC (p = 5.8 × 10−6). EOCRC acquires unique DNAm alterations at 234 loci. CpGs associated with ageing-associated drift were widely affected in EOCRC without needing the decades-long accrual of DNAm drift as commonly seen in intermediate- and late-onset CRCs. Accelerated ageing in normal mucosa from people with EOCRC potentially underlies the earlier age of diagnosis in CRC carcinogenesis.

Download Full-text

DNA methylation signatures and the contribution of age-associated methylomic drift to carcinogenesis in early-onset colorectal cancer

10.1101/2021.03.24.21254210 ◽

2021 ◽

Author(s):

Jihoon E. Joo ◽

Mark Clendenning ◽

Ee Ming Wong ◽

Christophe Rosty ◽

Khalid Mahmood ◽

...

Keyword(s):

Colorectal Cancer ◽

Dna Methylation ◽

Early Onset ◽

Age Of Onset ◽

Late Onset ◽

Normal Mucosa ◽

Accelerated Ageing ◽

Normal Colonic Mucosa ◽

Age Related ◽

Differentially Methylated Genes

AbstractBackgroundThe role of DNA methylation (DNAm) in the carcinogenesis of colorectal cancer (CRC) diagnosed <50years of age (early-onset CRC or EOCRC) is currently unknown. We investigated aberrant DNAm changes and the contribution of ageing-associated methylomic drift, and age acceleration to EOCRC carcinogenesis.MethodsGenome-wide DNAm profiling using the Infinium HM450K on 97 EOCRC tumour and 54 normal colonic mucosa samples was compared with: 1) intermediate-onset CRC (IOCRC; diagnosed between 50-70 years; 343 tumour and 35 normal); and 2) late-onset CRC (LOCRC; >70 years; 318 tumour and 40 normal). CpGs associated with age-related methylation drift were identified using a public dataset of 231 normal mucosa samples from people without CRC. DNAm-age was estimated using epiTOC2.ResultsCommon to all three age-of-onset groups, 88,385 (20% of all CpGs) CpGs were differentially methylated between tumour and normal mucosa. We identified 234 differentially methylated genes that were unique to the EOCRC group. In normal mucosa from people without CRC, we identified 28,154 CpGs that undergo ageing-related DNAm drift and of those, 65% were aberrantly methylated in EOCRC tumours. Based on the mitotic-based DNAm clock epiTOC2, we identified age acceleration in normal mucosa of people with EOCRC compared with normal mucosa from the IOCRC, LOCRC groups (p=3.7×10−16) and young people without CRC (p=5.8×10−6).ConclusionEOCRC acquires unique DNAm alterations at 234 loci. CpGs associated with ageing-associated drift were widely affected in EOCRC without needing the decades-long accrual of DNAm drift as commonly seen in intermediate- and late-onset CRCs. We found accelerated ageing in normal mucosa from people with EOCRC, as evidenced by a faster stem-cell division rate, potentially contributing to EOCRC carcinogenesis.

Download Full-text

NEONATAL SEPSIS AND IDENTIFICATION OF RISK FACTORS: STUDY IN AVBRH HOSPITAL SAWANGI

International Journal of Medical and Biomedical Studies ◽

10.32553/ijmbs.v3i6.1215 ◽

2019 ◽

Vol 3 (6) ◽

Author(s):

Pramod P. Singhavi

Keyword(s):

Risk Factors ◽

Neonatal Sepsis ◽

Early Onset ◽

Late Onset ◽

Signs And Symptoms ◽

Premature Rupture ◽

Maternal Risk ◽

Late Onset Sepsis ◽

Early Onset Sepsis ◽

Meconium Stained Amniotic Fluid

Introduction: India has the highest incidence of clinical sepsis i.e.17,000/ 1,00,000 live births. In Neonatal sepsis septicaemia, pneumonia, meningitis, osteomyelitis, arthritis and urinary tract infections can be included. Mortality in the neonatal period each year account for 41% (3.6 million) of all deaths in children under 5 years and most of these deaths occur in low income countries and about one million of these deaths are due to infectious causes including neonatal sepsis, meningitis, and pneumonia. In early onset neonatal sepsis (EOS) Clinical features are non-specific and are inefficient for identifying neonates with early-onset sepsis. Culture results take up to 48 hours and may give false-positive or low-yield results because of the antenatal antibiotic exposure. Reviews of risk factors has been used globally to guide the development of management guidelines for neonatal sepsis, and it is similarly recommended that such evidence be used to inform guideline development for management of neonatal sepsis. Material and Methods: This study was carried out using institution based cross section study . The total number neonates admitted in the hospital in given study period was 644, of which 234 were diagnosed for neonatal sepsis by the treating pediatrician based on the signs and symptoms during admission. The data was collected: Sociodemographic characteristics; maternal information; and neonatal information for neonatal sepsis like neonatal age on admission, sex, gestational age, birth weight, crying immediately at birth, and resuscitation at birth. Results: Out of 644 neonates admitted 234 (36.34%) were diagnosed for neonatal sepsis by the paediatrician based on the signs and symptoms during admission. Of the 234 neonates, 189 (80.77%) infants were in the age range of 0 to 7 days (Early onset sepsis) while 45 (19.23%) were aged between 8 and 28 days (Late onset sepsis). Male to female ratio in our study was 53.8% and 46% respectively. Out of total 126 male neonates 91(72.2%) were having early onset sepsis while 35 (27.8%) were late onset type. Out of total 108 female neonates 89(82.4%) were having early onset sepsis while 19 (17.6%) were late onset type. Maternal risk factors were identified in 103(57.2%) of early onset sepsis cases while in late onset sepsis cases were 11(20.4%). Foul smelling liquor in early onset sepsis and in late onset sepsis was 10(5.56%) and 2 (3.70%) respectively. In early onset sepsis cases maternal UTI, Meconium stained amniotic fluid, Multipara and Premature rupture of membrane was seen in 21(11.67%), 19 (10.56%), 20(11.11%) and 33 (18.33%) cases respectively. In late onset sepsis cases maternal UTI, Meconium stained amniotic fluid, Multipara and Premature rupture of membrane was seen in 2 (3.70%), 1(1.85%), 3 (5.56%) and 3 (5.56%) cases respectively. Conclusion: Maternal risk identification may help in the early identification and empirical antibiotic treatment in neonatal sepsis and thus mortality and morbidity can be reduced.

Download Full-text

Classification and Comparison of Early-onset and Late-onset Idiopathic Chronic Pancreatitis

Case Medical Research ◽

10.31525/ct1-nct03953937 ◽

2019 ◽

Author(s):

Keyword(s):

Chronic Pancreatitis ◽

Early Onset ◽

Late Onset ◽

Idiopathic Chronic Pancreatitis

Download Full-text

Faculty Opinions recommendation of DNA methylation profiling of human placentas reveals promoter hypomethylation of multiple genes in early-onset preeclampsia.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.3318956.3005054 ◽

2010 ◽

Author(s):

Sue Malcolm ◽

Sayeda Abu-Amero

Keyword(s):

Dna Methylation ◽

Early Onset ◽

Multiple Genes ◽

Dna Methylation Profiling ◽

Early Onset Preeclampsia ◽

Methylation Profiling

Download Full-text

Faculty Opinions recommendation of Cardiovascular disease risk factors after early-onset preeclampsia, late-onset preeclampsia, and pregnancy-induced hypertension.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725298358.793542862 ◽

2018 ◽

Author(s):

Andrew Shennan ◽

Kate Duhig

Keyword(s):

Risk Factors ◽

Cardiovascular Disease ◽

Early Onset ◽

Disease Risk ◽

Late Onset ◽

Cardiovascular Disease Risk ◽

Cardiovascular Disease Risk Factors ◽

Pregnancy Induced Hypertension ◽

Induced Hypertension ◽

Early Onset Preeclampsia

Download Full-text

Faculty Opinions recommendation of Risk of non-fatal cardiovascular diseases in early-onset versus late-onset type 2 diabetes in China: a cross-sectional study.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.726040074.793514750 ◽

2016 ◽

Author(s):

Carlos Aguilar-Salinas

Keyword(s):

Type 2 Diabetes ◽

Cardiovascular Diseases ◽

Early Onset ◽

Late Onset ◽

Cross Sectional Study ◽

Sectional Study ◽

Cross Sectional ◽

Onset Type

Download Full-text

Exploring the Role of Aggregated Proteomes in the Pathogenesis of Alzheimer’s Disease

Current Protein and Peptide Science ◽

10.2174/1389203721666200921152246 ◽

2020 ◽

Vol 21 (12) ◽

pp. 1164-1173

Author(s):

Siju Ellickal Narayanan ◽

Nikhila Sekhar ◽

Rajalakshmi Ganesan Rajamma ◽

Akash Marathakam ◽

Abdullah Al Mamun ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Amyloid Precursor Protein ◽

Early Onset ◽

Late Onset ◽

Precursor Protein ◽

Brain Disorder ◽

Amyloid Aβ ◽

T Tau

: Alzheimer’s disease (AD) is a progressive brain disorder and one of the most common causes of dementia and death. AD can be of two types; early-onset and late-onset, where late-onset AD occurs sporadically while early-onset AD results from a mutation in any of the three genes that include amyloid precursor protein (APP), presenilin 1 (PSEN 1) and presenilin 2 (PSEN 2). Biologically, AD is defined by the presence of the distinct neuropathological profile that consists of the extracellular β-amyloid (Aβ) deposition in the form of diffuse neuritic plaques, intraneuronal neurofibrillary tangles (NFTs) and neuropil threads; in dystrophic neuritis, consisting of aggregated hyperphosphorylated tau protein. Elevated levels of (Aβ), total tau (t-tau) and phosphorylated tau (ptau) in cerebrospinal fluid (CSF) have become an important biomarker for the identification of this neurodegenerative disease. The aggregation of Aβ peptide derived from amyloid precursor protein initiates a series of events that involve inflammation, tau hyperphosphorylation and its deposition, in addition to synaptic dysfunction and neurodegeneration, ultimately resulting in dementia. The current review focuses on the role of proteomes in the pathogenesis of AD.

Download Full-text