Background: The concept of CpG island methylator phenotype (CIMP) is not universally accepted. Even if specific clinicopathological features have been associated with CIMP, investigators often failed to demonstrate a ...Background: The concept of CpG island methylator phenotype (CIMP) is not universally accepted. Even if specific clinicopathological features have been associated with CIMP, investigators often failed to demonstrate a bimodal distribution of the number of methylated markers, which would suggest CIMP as a distinct subtype of colorectal cancer. Previous studies primarily used methylation specific polymerase chain reaction which might detect biologically insignificant low levels of methylation. Aim: To demonstrate a distinct genetic profile of CIMP colorectal cancer using quantitative DNA methylation analysis that can distinguish high from low levels of DNA methylation. Materials and methods: We developed quantitative real time polymerase chain reaction (MethyLight) assays and measured DNA methylation (percentage of methylated reference) of five carefully selected loci (promoters of CACNA1G,CDKN2A (p16), CRABP1, MLH1, and NEUROG1) in 460 colorectal cancers from large prospective cohorts. Results: There was a clear bimodal distribution of 80 microsatellite instability-high (MSI-H) tumours according to the number of methylated promoters, with no tumours showing 3/5 methylated loci. Thus we defined CIMP as having ≥4/5 methylated loci, and 17%(78) of the 460 tumours were classified as CIMP. CIMP was significantly associated with female sex, MSI, BRAF mutations, and wild-type KRAS.Both CIMP MSI-H tumours and CIMP microsatellite stable (MSS) tumours showed much higher frequencies of BRAF mutations (63%and 54%) than non-CIMP counterparts (non-CIMP MSI-H (0%, p < 10-5) and non-CIMP MSS tumours (6.6%, p< 10-4), respectively). Conclusion: CIMP is best characterised by quantitative DNA methylation analysis. CIMP is a distinct epigenotype of colorectal cancer and may be less frequent than previously reported.展开更多
Background: Isolated left venticular noncompaction(IVNC) is a rare congenital heart disease charactrized by a pattern of an excessively prominent trabecular meshwork with deep intertrabecular recesses. Heart rate vari...Background: Isolated left venticular noncompaction(IVNC) is a rare congenital heart disease charactrized by a pattern of an excessively prominent trabecular meshwork with deep intertrabecular recesses. Heart rate variability(HRV) has been reported to be impaired in various heart diseases, though little is known regarding HRV in adult patients with IVNC. Methods: We measured spectral components of HRV using fast Fourier transformation of 24h Holter recordings in 10 adult patients with IVNC, 40 patients with myocardial infarction(MI), 40 patients with hypertrophic cardiomyopathy(HCM) and 40 healthy controls. Results: The low frequency component and the high frequency component of HRV were lower in IVNC patients tahn those in controls(265±213 ms2 vs. 469±195 ms2, p< 0.01; 80±51 ms2 vs. 185±126 ms2, p< 0.01). Furthermore, 3 IVNC patients with a previous history of heart failure exhibited more decreased HRV(low frequency, 75±56 ms2; high frequency, 39±18 ms2). Contrary, the ratio of low frequency to high frequency component was higher in patients with IVNC than controls(3.5±0.5 vs. 3.2±0.3, p< 0.05). The degree of impaired HRV was severest in MI patients, intermediate in IVNC patients and mildest in HCM patients compared with controls. Conclusions: HRV is impaired in adult patients with IVCN, especially in patients with a previous history of heart failure, suggesting vagal withdrawal or sympathetic enhancement. HRV in IVNC adults is less impaired than in MI patients, and more impaired than in HCM patients of our cohort.展开更多
Sinus cycle length has been reported to fluctuate after a ventricular premature beat(VPB). The purpose of this study was to assess the short-term fluctuations of sinus cycle length in patients with hypertrophic cardio...Sinus cycle length has been reported to fluctuate after a ventricular premature beat(VPB). The purpose of this study was to assess the short-term fluctuations of sinus cycle length in patients with hypertrophic cardiomyopathy(HCM) and prior myocardial infarction(MI). Methods: The relative deviation of RR intervals from the mean of the last two RR intervals preceding a VPB were calculated during the 20 subsequent beats following the VPB from Holter recordings in 92 patients with non-obstructive HCM, 57 patients with prior MI and 54 healthy controls. Results: In controls, the deviations of the RR intervals were negative for several beats after a VPB and subsequently changed to positive before returning to the baseline. Similar changes in RR intervals following a VPB were exhibited in HCM patients; however, the late positive deviations of RR intervals were more marked than in controls. By contrast, in patients with prior MI, the early negative deviations of RR intervals were smaller compared with controls, and the deviations returned to the baseline without incidence of the positive changes. Conclusions: Short-term fluctuations in sinus cycle length after a VPB differed exclusively among HCM patients, prior MI patients, and healthy controls.展开更多
文摘Background: The concept of CpG island methylator phenotype (CIMP) is not universally accepted. Even if specific clinicopathological features have been associated with CIMP, investigators often failed to demonstrate a bimodal distribution of the number of methylated markers, which would suggest CIMP as a distinct subtype of colorectal cancer. Previous studies primarily used methylation specific polymerase chain reaction which might detect biologically insignificant low levels of methylation. Aim: To demonstrate a distinct genetic profile of CIMP colorectal cancer using quantitative DNA methylation analysis that can distinguish high from low levels of DNA methylation. Materials and methods: We developed quantitative real time polymerase chain reaction (MethyLight) assays and measured DNA methylation (percentage of methylated reference) of five carefully selected loci (promoters of CACNA1G,CDKN2A (p16), CRABP1, MLH1, and NEUROG1) in 460 colorectal cancers from large prospective cohorts. Results: There was a clear bimodal distribution of 80 microsatellite instability-high (MSI-H) tumours according to the number of methylated promoters, with no tumours showing 3/5 methylated loci. Thus we defined CIMP as having ≥4/5 methylated loci, and 17%(78) of the 460 tumours were classified as CIMP. CIMP was significantly associated with female sex, MSI, BRAF mutations, and wild-type KRAS.Both CIMP MSI-H tumours and CIMP microsatellite stable (MSS) tumours showed much higher frequencies of BRAF mutations (63%and 54%) than non-CIMP counterparts (non-CIMP MSI-H (0%, p < 10-5) and non-CIMP MSS tumours (6.6%, p< 10-4), respectively). Conclusion: CIMP is best characterised by quantitative DNA methylation analysis. CIMP is a distinct epigenotype of colorectal cancer and may be less frequent than previously reported.
文摘Background: Isolated left venticular noncompaction(IVNC) is a rare congenital heart disease charactrized by a pattern of an excessively prominent trabecular meshwork with deep intertrabecular recesses. Heart rate variability(HRV) has been reported to be impaired in various heart diseases, though little is known regarding HRV in adult patients with IVNC. Methods: We measured spectral components of HRV using fast Fourier transformation of 24h Holter recordings in 10 adult patients with IVNC, 40 patients with myocardial infarction(MI), 40 patients with hypertrophic cardiomyopathy(HCM) and 40 healthy controls. Results: The low frequency component and the high frequency component of HRV were lower in IVNC patients tahn those in controls(265±213 ms2 vs. 469±195 ms2, p< 0.01; 80±51 ms2 vs. 185±126 ms2, p< 0.01). Furthermore, 3 IVNC patients with a previous history of heart failure exhibited more decreased HRV(low frequency, 75±56 ms2; high frequency, 39±18 ms2). Contrary, the ratio of low frequency to high frequency component was higher in patients with IVNC than controls(3.5±0.5 vs. 3.2±0.3, p< 0.05). The degree of impaired HRV was severest in MI patients, intermediate in IVNC patients and mildest in HCM patients compared with controls. Conclusions: HRV is impaired in adult patients with IVCN, especially in patients with a previous history of heart failure, suggesting vagal withdrawal or sympathetic enhancement. HRV in IVNC adults is less impaired than in MI patients, and more impaired than in HCM patients of our cohort.
文摘Sinus cycle length has been reported to fluctuate after a ventricular premature beat(VPB). The purpose of this study was to assess the short-term fluctuations of sinus cycle length in patients with hypertrophic cardiomyopathy(HCM) and prior myocardial infarction(MI). Methods: The relative deviation of RR intervals from the mean of the last two RR intervals preceding a VPB were calculated during the 20 subsequent beats following the VPB from Holter recordings in 92 patients with non-obstructive HCM, 57 patients with prior MI and 54 healthy controls. Results: In controls, the deviations of the RR intervals were negative for several beats after a VPB and subsequently changed to positive before returning to the baseline. Similar changes in RR intervals following a VPB were exhibited in HCM patients; however, the late positive deviations of RR intervals were more marked than in controls. By contrast, in patients with prior MI, the early negative deviations of RR intervals were smaller compared with controls, and the deviations returned to the baseline without incidence of the positive changes. Conclusions: Short-term fluctuations in sinus cycle length after a VPB differed exclusively among HCM patients, prior MI patients, and healthy controls.
