
IndraLab
Statements
sparser
"To further explore the molecular mechanisms between altered TSGs promoter methylation and overexpression of DNMTs protein, we performed a tissue chromatin-immunoprecipitation polymerase chain reaction assay for lung tumors and showed that the methylated FHIT, p16(INK4a) and RARbeta promoters were bound by both DNMT protein and methyl-CpG-binding protein 2."
sparser
"Thus, Fhit is inactivated at an early stage in the development of ESCC ( xref ); FHIT gene promoter methylation has been linked to cigarette smoking ( xref , xref ), and ESCC may be associated with loss of the Fhit protein expression along with alcohol consumption ( xref , xref )."
sparser
"Methylation of CDH1, FHIT, LAMC2, RASSF1A, TIMP3, SFRP1, SOX9, PMF1 and RUNX3 genes is associated with poor survival in muscle-invasive bladder cancer.[ xref xref ] Methylation of RASSF1A and HOXB2 were associated with bladder tumor stage, grade and tumor progression.[ xref xref ] Several studies have examined methylation markers in the urine of patients with bladder cancer."
sparser
"Finally, 14 articles with 1,345 controls and 945 cases for FHIT expression were involved, while 3 articles with 75 controls and 124 cases for FHIT methylation were included.. xref – xref According to the extracted information of included studies, the frozen liver cancer tissues and normal or adjacent liver tissues were obtained through surgical operation to extract the DNA and detect the expression of FHIT and methylation of FHIT gene."
sparser
"We performed a comprehensive analysis on FHIT gene methylation and expression in uncultured peripheral blood mononuclear cells (PBMC) isolated from healthy volunteer donors (HD), HTLV-I infected asymptomatic carriers (AC), and HTLV-I infected individuals diagnosed with tropical spastic paraparesis/HTLV- I-associated myelopathy patients (TSP/HAM) and adult T-cell leukemia (ATL)."
sparser
"In this study, DNA methylation of FHIT, serum folate level and HPV16 status were measured using methylation-specific polymerase chain reaction (MSP), radioimmunoassay (RIA) and polymerase chain reaction (PCR), respectively, in 310 women with a diagnosis of normal cervix (NC, n=109), cervical intraepithelial neoplasia (CIN, n=101) and squamous cell carcinoma of the cervix (SCC, n=101)."
sparser
"Inactivation of FHIT by promoter hypermethylation plays an important role in tumorigenesis in several types of tumors including NSCLC. xref , xref – xref To date, there have been some studies describing the methylation status of FHIT in NSCLC; however, the roles of methylation of FHIT in NSCLC and clinical significance have not been thoroughly investigated."
sparser
"Yet another group reported differential methylation of CDH1 , DAPK1 , CDKN2A , MGMT , ICDKN2B , FHIT , APC , RASSF1 , GSTP1 , RARB , and TP73 in bladder cancer specimens, with schistosomiasis-associated specimens featuring more differentially methylated genes than those not associated with this infection [ xref ]."
sparser
"Of the remaining 28 articles, 3 did not have the frequency of FHIT expression in case group and control group, 2 contained duplicate data, the samples of 4 were inappropriate, and 2 publications were about FHIT gene methylation and did not have sufficient frequency of FHIT gene methylation."
sparser
"Our results indicate that: (1) aberrant, widespread methylation of CpG islands increases with the histological progression of serrated adenomas; (2) methylation of SLC5A8 is an early event; and (3) additional methylation of the p16, p14, MGMT, TIMP3, and FHIT genes are important tumorigenic steps in the serrated neoplasia pathway."
sparser
"Interaction analysis showed that the ORs only with FHIT methylation (OR=11.47) or only with HPV 16 positive (OR=4.63) or with serum folate level lower than 3.19ng/ml (OR=1.68) in SCC group were all higher than the control status of HPV 16 negative and FHIT unmethylation and serum folate level more than 3.19ng/ml (OR=1)."
sparser
"The promoter methylation of DAPK1, FHIT, MGMT, and CDKN2A was investigated by using a methylation-specific polymerase chain reaction in 53 specimens of cervical cancer (42 squamous cell carcinoma, 11 adenocarcinoma), 22 specimens of intraepithelial neoplasia tissues, and 24 control normal cervical tissue specimens."
sparser
"Nicotine administration in human bronchial epithelial cells significantly upregulates several genes particularly associated with activation of mitogen activated protein kinase (MAPK).[ xref ] Nicotine increases methylation of the fragile histidine triad (FHIT) gene resulting in decreased FHIT and increased deoxyribonucleic acid (DNA) methyltransferase (DNMT) 3a expression.[ xref ] Notably, removal of nicotine restores normal methylation patterns and expression suggesting the effect of nicotine is reversible."
sparser
"Univariate analysis revealed adverse prognostic factors: FHIT gene methylation (P = 0.028), poor performance status (I to IV, P = 0.002), anemia (< or =8.5 g/dL, P = 0.007), hypoalbuminemia (< or =3.5 g/dL, P < 0.002), high serum C-reactive protein levels (>0.5 mg/dL, P = 0.002), elevated beta-2-microglobulin serum levels (>6.5 mg/L, P < 0.001), and treatments not including autologous peripheral blood stem cell transplantation (auto-PBSCT) (P = 0.007)."
sparser
"A relatively high frequency of CpG promoter methylation (52%) was found only in hTERT, with low frequency of methylation (<15%) in p16INK4a , TIMP3 , RASFF1 , and RARB , and no methylation in FHIT and APC .[ xref ] Given the presence of promoter methylation of APC , RASSF1 , and RARB in cutaneous melanoma, these findings suggest that cutaneous and UM likely undergo different epigenetic changes."
sparser
"In family A, the father died from ATL disease; however, we were able to obtain samples from a sibling, a wife, and three children that were all asymptomatic carriers for HTLV-I. Examination of FHIT methylation in all asymptomatic carriers of the family showed strong FHIT methylation in the sibling and son, with lower methylation in the 2nd son and daughter."
sparser
"Interestingly, difference was found between Asian (3.50, 95% CI: 1.50 - 8.14, P = 0.005) and Caucasian population (2.55, 95% CI: 0.86 - 7.57, P = 0.09) subgroup (Figure xref ), and the differential methylation in Caucasian population is not significant, indicating that diagnostic ability of FHIT methylation might be limited in Caucasian population."
sparser
"Subgroup analysis showed that FHIT methylation is significantly relevant to NSCLC in Asians (OR = 3.50, 95% CI: 1.50 - 8.14) but not in Caucasian population (OR = 2.55, 95% CI: 0.86 - 7.57), indicating that aberrant methylation of FHIT can be a diagnostic biomarker for NSCLC in Asian population."
sparser
"Recent evidence indicates that inactivation of FHIT by promoter hypermethylation plays an important role in tumorigenesis in several types of tumors including BC. xref – xref However, the reported correlation between FHIT methylation and clinicopathological features in BC was inconsistent."
sparser
"In a study of OSCCs associated with betel and/or tobacco use ( xref ), 28% of samples exhibited FHIT promoter methylation, and 36% of cancers and 50% of premalignant lesions showed aberrant RT–PCR products, suggesting that FHIT aberration could be an early event in oral carcinogenesis."
sparser
"Due to the previous limitations, we strongly recommend to use more advanced methylation detection methods, like WGBS (whole genome bisulfite sequencing) and RRBS (restricted region bisulfite sequencing), to explore the association between FHIT promoter methylation and NSCLC with larger sample sizes."
sparser
"We analyzed ATL samples with unmethylated or weak methylated FHIT and found only 1 patient with a deletion of exon 5, and none with deletions in exon 8, demonstrating that the majority of unmethylated ATL patients’ sample have an intact FHIT gene, with no loss of FHIT integrity in these regions (Suppl xref )."
sparser
"Our study suggests that tumor-specific methylation of the p16, RASSF1A, H-cadherin, and RARbeta genes may be a valuable biomarker for the early detection of NSCLC in bronchial lavage, and that the age-related methylation of FHIT gene in the normal bronchial epithelium is related to the exposure to tobacco smoke."
sparser
"Recently, in paired HNSCC primary A) and recurrent or metastatic (B) UMSCC-11A/11B, UMSCC-17A/17B, and UMSCC-81A/81B cell lines, using MS-MLPA, we identified nine genes, TIMP3, APC, KLK10, TP73, CDH13, IGSF4, FHIT, ESR1 , and DAPK1 that were aberrantly methylated in paired HNSCC primary A) and recurrent or metastatic (B) UMSCC-11A/11B, UMSCC-17A/17B, and UMSCC-81A/81B cell lines[ xref ]."
sparser
"Among premenopausal women, compared with Stage 0 cases, cases of invasive cancer were more likely to have increased methylation of RARB (Stage I OR = 4.7, 95% CI: 1.1-19.0; Stage IIA/IIB OR = 9.7, 95% CI: 2.4-39.9; Stage III/IV OR = 5.6, 95% CI: 1.1-29.4) and lower methylation of FHIT (Stage I OR = 0.2, 95% CI: 0.1-0.9; Stage IIA/IIB OR = 0.2, 95% CI: 0.1-0.8; Stage III/IV OR = 0.6, 95% CI: 0.1-3.4)."
sparser
"It remains highly unlikely due to several observations: 1- FHIT methylation was independent of proviral load, 2- non-infected cells (CD25- and CD19-) harbored methylated FHIT to the same extend as infected cells (arguing against the dilution effect), 3- gDNA extracted from nails was positive for FHIT methylation, and 4- the low number of FHIT methylated samples in asymptomatic carriers and TSP/HAM patients, who are infected with HTLV-I. We found approximately, 22% of acute and 11% of chronic ATL patient samples had unmethylated FHIT."
sparser
"To determine if in rat tissues: (1) Fhit methylation status is related to expression levels and (2) Fhit methylation patterns were tissue- or carcinogen-specific, we examined Fhit methylation status and expression levels in DMBA- and MNU-induced benign and malignant mammary tumors."
sparser
"These results suggest that in ATL families, 1- FHIT methylation is higher in descendants with methylated FHIT (FHIT methylation = 100%) than in normal asymptomatic carriers (FHIT methylation = 5.62%), 2- children of ATL parents have strongly methylated FHIT regardless of whether they are asymptomatic carriers or have ATL, 3- FHIT methylation may be passed down from parents to children through additive or non-additive genetic effects."
sparser
"In order to demonstrate the relationship between methylation of fragile histidine triad (FHIT) and T-cadherin/H-cadherin (CDH13) genes and liver cancer, the methylation status of FHIT and CDH13 was detected in healthy individuals and in Mongolian and Han patients with liver cancer."
sparser
"To test whether aberrant methylation of the FHIT gene may play a role in pediatric leukemia, we assessed the FHIT methylation status of 10 leukemia cell lines and 190 incident population-based cases of childhood acute lymphocytic and myeloid leukemias using methylation-specific PCR."
sparser
"When compared to other viral lymphomas associated with infection by KSHV, HCV or EBV, ATL lymphoma patients presented with a higher proportion of methylated FHIT (Suppl xref ); however, the limited number of samples precludes this from being statistically significant and will need to be expanded upon in future studies."
sparser
"Recently, using a multi-candidate gene approach, the Methylation Specific Multiplex Ligation-dependent Probe Amplification (MS-MLPA) assay (MS-MLPA, xref ) ( xref , xref ), we identified nine genes, TIMP3, APC, KLK10, TP73, CDH13, IGSF4, FHIT , ESR1 , and DAPK1 that were aberrantly methylated in paired HNSCC primary A) and recurrent or metastatic (B) UMSCC-11A/11B, UMSCC-17A/17B, and UMSCC-81A/81B cell lines ( xref – xref )( xref )."
sparser
"FHIT, mutated in four out of five liver metastases, is believed to be a tumor suppressor involved in purine metabolism and lower FHIT expression/promoter methylation is associated with poor outcome in non-small cell lung and breast cancer and metastasis in colon cancer xref , xref , xref ."
sparser
"Wu et al [ xref ] reported that FHIT was highly methylated in Hela, C33A and Siha cervical cancer cells, and that aberrant methylation of the FHIT gene might be a key mechanism for cervical tumorigenesis, which could be reactivated and whose tumor suppressing function could be restored by treatment of demethylating agent."
sparser
"Our main findings are as follows: (a) methylation was completely absent in control tissues; (b) the frequencies of methylation for all of the genes except hMLH1 were >20% in cervical cancers; (c) aberrant methylation commenced early during multistage pathogenesis and methylation of at least one gene was noted in 30% of the nondysplasia/low-grade CIN group; (d) an increasing trend for methylation was seen with increasing pathological change; (e) methylation of RARbeta and GSTP1 were early events, p16 and MGMT methylation were intermediate events, and FHIT methylation was a late, tumor-associated event; and (f) methylation occurred independently of other risk factors including papillomavirus infection, smoking history, or hormone use."
sparser
"The promoter methylation of DAPK1, FHIT, MGMT, and CDKN2A in cervical cancer vs. intraepithelial neoplasia vs. normal cervical tissue was 75.5 vs. 31.8 vs. 4.2 % (p < 0.0001), 66.0 vs. 59.1 vs. 25.0 % (p = 0.0033), 34.0 vs. 27.3 vs. 20.8 % (p = 0.76), and 17.0 vs. 31.8 vs. 8.3 % (p = 0.11), respectively."
sparser
"Haroun et al observed that the methylation frequencies of the genes tested in non-small cell lung carcinoma specimens were 53.6% for FHIT . xref Jeong et al evaluated the methylation of FHIT in 60 BC samples; FHIT methylation was detected in 96.7% and the positive expression rate of FHIT in 87.3% of the patients. xref Our data and previous studies indicate that FHIT promoter hypermethylation is a useful diagnostic biomarker of BC."
sparser
"Since genetic alterations were not frequently observed in DNA corresponding to the FHIT gene in renal tumours, to elucidate the mechanism of FHIT gene silencing we examined 22 paired samples of clear cell renal carcinoma and non-malignant renal tissue for the methylation of the FHIT 5'CpG island by methylation-specific PCR."
sparser
"For example, in patients with acute leukemia, which compared with the dual vacuity of Qi and Yin syndrome, ID4 gene methylation is more likely to occur in patients with toxic hot flaming syndrome and static blood and binding phlegm syndrome.[ xref ]Differences in methylation of HLA-DRB1 and ADAMTS9, NUDT1 and YES1, and APOA5 and PRKCZ genes might be related to hepatitis B and cirrhosis with damp-heat brewing internally syndrome, spleen deficiency, and exuberant phlegm and liver-kidney yin depletion.[ xref ]The methylation of the promoter regions of FHIT, MAP2K6, WNT5B, CSNK1D, and FRAT2 genes on CpG island was associated with kidney yang vacuity.[ xref ]At present, the research of molecular mechanism of DNA methylation is still at the initial stage."
sparser
"Methylation of 5'-CpG islands in 10 normal cervical squamous epithelial tissues, and 40 cervical cancer tissues was detected with methylation specific polymerase chain reaction (MSP), protein expression of FHIT was detected with immunohistochemistry, and their correlations with clinicopathologic features of cervical cancer were statistically analyzed. (1) The 5'-CpG islands methylation rate of FHIT gene in cervical cancer tissues was 40.0% (16/40), while no methylation of FHIT gene was found in normal cervical tissues. (2) The methylation rates of FHIT gene in cervical cancer of stage I was 14.3% (2/14), significantly lower than that in cervical cancer of stage II (56.5%, 13/23) (P<0.05). (3) Expression of FHIT protein in cervical cancer was 33.0% (12/40), significantly lower than that in normal cervical tissue (100%, 10/10) (P<0.05)."
sparser
"Recently, using a multi-candidate gene assay, xref we identified nine genes, TIMP3, APC, KLK10, TP73, CDH13, IGSF4, FHIT , ESR1 , and DAPK1 that were aberrantly methylated in paired HNSCC primary and recurrent or metastatic cell lines xref The most frequently hypermethylated genes were APC and IGSF4 observed in 3/6 cell lines, and TP73 and DAPK1 observed in 2/6."
sparser
"The difference is possibly due to the diagnosis time for ALL, which leads to the alteration of FHIT methylation frequency, as numerous studies have demonstrated that FHIT methylation is an accumulated process and different diagnosis times exhibit different methylation frequencies ( xref – xref )."
sparser
"Koga et al. reported that EGFR mutation and CHFR hypermethylation in lung adenocarcinoma are mutually exclusive [ xref ], Similarly, Suzuki et al. reported that lung tumors with wildtype EGFR show more prevalent hypermethylation of p16 (34% vs. 16%) and SPARC (60% vs. 37%) genes compared to EGFR mutant tumors [ xref ], Yanagawa et al. also compared the relationship between methylation of 10 cancer-related genes and mutations of EGFR, KRAS, and TP53 in 62 lung adenocarcinoma cases from smokers and never-smokers and found that the prevalence for methylation of FHIT, RASSF1A, and RUNX3 genes in EGFR mutant tumors was significantly lower compared to EGFR wild-type tumors , In contrast, the significantly higher rate of TOX3 methylation in EGFR mutant than wildtype tumors demonstrates that aberrant methylation is not always inversely associated to EGFR mutation."
sparser
"Multivariate analysis identified FHIT gene methylation [hazard ratio (HR) 1.722, 95% confidence interval (CI) 1.150-2.603, P = 0.009], elevated beta-2-microglobulin serum levels (>6.5 mg/L, HR 2.005, 95% CI 1.035-3.937, P = 0.004), and treatments not including auto-PBSCT are independent predictive variables."
sparser
"For instance, Lin et al found that the frequency of FHIT gene hypermethylation in myelodysplastic syndrome patients was higher than in normal persons. xref Moreover, it has been reported that the loss of FHIT was associated with the risk of gastric cancer, breast cancer, and lung cancer. xref – xref And the aberrant methylation of FHIT gene had a significant association with the clinical stage and other clinical features."
sparser
"Promoter methylation of the CDH1 , RARB , FHIT , and MGMT genes was noted only in SCC, whereas the AC exhibited significantly higher frequency of promoter methylation of HIC1 (60% in AC vs. 15.6% in SCC), APC (80% in AC vs. 6.5% in SCC), and BRCA1 (40% in AC vs. 3.9% in SCC) (Table xref )."
sparser
"We have also used an epigenome-wide scan of DNAm in the placenta to demonstrate relationships between methylation of the FHIT and ANDKR11 genes, which had been previously linked to neurodevelopmental and behavioral outcomes, and performance on the NNNS attention scale in a cohort of term newborns xref ."