1.
Novel FBN1 Heterozygous Mutations Identified in Chinese Families with Marfan Syndrome.
Yao, X, Wu, J, Chen, J
Annals of clinical and laboratory science. 2019;(4):539-545
Abstract
OBJECTIVE To detect the mutations in the fibronectin-1 gene (FBN1) of four Chinese families with autosomal dominant Marfan syndrome (MFS), and to discuss the associated phenotypes. METHODS We examined ten patients, and five non-carriers, in four Chinese families with autosomal dominant Marfan syndrome (MFS) for FBN1 mutations. Comprehensive physical, ophthalmic, and cardiovascular examinations were performed on the family members. The FBN1 gene was amplified with PCR from the DNA of the patients and their relatives. The amplified products were sequenced and compared with a reference sequence from the GenBank database. The changes in the structure and function of the protein caused by the amino acid substitution were investigated with a bioinformatics analysis. RESULTS In our study, sequencing FBN1 revealed three novel mutations, and one mutation which was found earlier in 2012. One of the novel mutations is c.649T>C in exon 7, which results in the substitution tryptophan by arginine at codon 217 (p.Trp217Arg), the other is a splice defect in intron 39 (c.4816+1G>A), and the third one is c.407G>T in exon 5, which altered an amino acid at residue 136 from Cysteine to Phenylalanine (p.Cys136Phe). The recurrent mutation was c.4151T>C in exon 34, resulting in methionine being replaced by threonine (p.Met1384Thr). The occurrence of the mutations correlated strongly with the phenotypes of the patients, and no mutation was detected in the normal relatives of the affected patients. CONCLUSIONS In this study, three novel and a recurrent FBN1 mutations were detected. The results expand the mutation spectrum of FBN1, helping in the study of molecular pathogenesis of MFS and Marfan-related disorders.
2.
Mutational Profiles Reveal an Aberrant TGF-β-CEA Regulated Pathway in Colon Adenomas.
Chen, J, Raju, GS, Jogunoori, W, Menon, V, Majumdar, A, Chen, JS, Gi, YJ, Jeong, YS, Phan, L, Belkin, M, et al
PloS one. 2016;(4):e0153933
Abstract
Mutational processes and signatures that drive early tumorigenesis are centrally important for early cancer prevention. Yet, to date, biomarkers and risk factors for polyps (adenomas) that inordinately and rapidly develop into colon cancer remain poorly defined. Here, we describe surprisingly high mutational profiles through whole-genome sequence (WGS) analysis in 2 of 4 pairs of benign colorectal adenoma tissue samples. Unsupervised hierarchical clustered transcriptomic analysis of a further 7 pairs of adenomas reveals distinct mutational signatures regardless of adenoma size. Transitional single nucleotide substitutions of C:G>T:A predominate in the adenoma mutational spectrum. Strikingly, we observe mutations in the TGF-β pathway and CEA-associated genes in 4 out of 11 adenomas, overlapping with the Wnt pathway. Immunohistochemical labeling reveals a nearly 5-fold increase in CEA levels in 23% of adenoma samples with a concomitant loss of TGF-β signaling. We also define a functional role by which the CEA B3 domain interacts with TGFBR1, potentially inactivating the tumor suppressor function of TGF-β signaling. Our study uncovers diverse mutational processes underlying the transition from early adenoma to cancer. This has broad implications for biomarker-driven targeting of CEA/TGF-β in high-risk adenomas and may lead to early detection of aggressive adenoma to CRC progression.
3.
Precore mutation of hepatitis B virus may contribute to hepatocellular carcinoma risk: evidence from an updated meta-analysis.
Liao, Y, Hu, X, Chen, J, Cai, B, Tang, J, Ying, B, Wang, H, Wang, L
PloS one. 2012;(6):e38394
Abstract
BACKGROUND Studies focused on the correlation of mutations in the genome of Hepatitis B Virus (HBV) like Pre-S mutation, Basal Core promoter (BCP), Enhancer II (EnhII), especially Precore mutation, with the risk of hepatocellular carcinoma (HCC) have triggered stiff controversies. With an increasing number of studies in this field recently, we conducted this meta-analysis to appraise the correlations. METHODS We searched the commonly used databases both in English and Chinese till February 1(st), 2012. Meta-analysis was performed in fixed/random-effects models using STATA 10.0. Publication bias was examined through Egger's test and Begg's funnel plot. RESULTS In total, 85 case-control studies were included involving 16745 HBV-infected patients, of whom 5781 had HCC. Statistically significant correlations were observed in Precore mutation G1896A (OR = 1.46, 95% confidence interval [CI] = 1.15-1.85, P(OR) = 0.002), G1899A (OR = 3.13, 95%CI = 2.38-4.13, P(OR)<0.001) and Pre-S mutation especially Pre-S1 deletion (OR = 2.94, 95%CI = 2.22 to 3.89) and Pre-S2 deletion (OR = 3.02, 95%CI = 2.03 to 4.50). Similar correlation existed between BCP double mutation A1762T/G1764A, T1753V, C1653T and HCC. In subgroup analysis, the Asians, genotype C or HBeAg positive patients with certain above mutations may be more susceptible to HCC. Besides, the mutations like G1896A and BCP double mutation may be associated with the progression of the liver diseases. CONCLUSIONS Precore mutation G1896A, G1899A, deletions in Pre-S region as well as the other commonly seen mutations correlated with the increased risk of HCC, especially in Asians and may predict the progression of the liver disease.