Paediatric hepatocellular carcinoma in tight junction protein 2 (TJP2) deficiency

Vij, Mukul; Shanmugam, Naresh; Reddy, Mettu Srinivas; Sankaranarayanan, Srinivas; Rela, Mohamed

doi:10.1007/s00428-017-2204-1

Cited by 35 publications

(23 citation statements)

References 19 publications

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“…Xu et al (52) identified that RAB11A was upregulated in ESCC and may serve a critical role in the development of ESCC. Other studies have demonstrated that KAT2B, CTNNA1 and TJP2 are important in multiple tumor types, including hepatocellular carcinoma, cervical cancer and breast cancer (53–55), however their roles in ESCC are not clear. In the current study, these three genes were targeted by the differentially expressed miRNAs in Kazakh ESCC, which suggests that they may also serve an important role in the development of ESCC.…”

Section: Discussionmentioning

confidence: 99%

Identifying the differentially expressed microRNAs in esophagus squamous cell carcinoma of Kazakh patients in Xinjiang

et al. 2019

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Despite improvements in diagnosis and treatment, the survival of patients with advanced stages of esophageal squamous cell carcinoma (ESCC) remains poor. Therefore, novel biomarkers that can assist with early detection of ESCC are required. In the present study, three paired ESCC and normal esophageal tissue samples from Xinjiang Kazakh patients were obtained and microRNA (miRNA) microarray analysis was used to detect the differentially-expressed miRNAs. The target genes of the identified miRNAs were predicted using miRWalk software. A total of 23 miRNAs were differently expressed in Kazakh patients with ESCC. Gene Ontology enrichment analysis demonstrated that the upregulated miRNAs were predominantly associated with the ‘vesicle’ and ‘membrane-bounded vesicle’ terms, while the downregulated miRNAs were primarily associated with the term ‘negative regulation of integrin-mediated signaling pathway’. The most highly enriched Kyoto Encyclopedia of Genes and Genomes pathway for the differentially-expressed miRNAs was ‘Endocrine and other factor-regulated calcium reabsorption’. Protein-protein interaction network analysis revealed that IQ motif containing GTPase activating protein 1, RAB11A, lysine acetyltransferase 2B, catenin α 1 and tight junction protein 2 were hub genes of the network. In conclusion, a number of differentially-expressed miRNAs were identified in ESCC tissues samples from Xinjiang Kazakh patients, which may improve the understanding of the processes of tumorigenesis and development.

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Section: Discussionmentioning

confidence: 99%

Identifying the differentially expressed microRNAs in esophagus squamous cell carcinoma of Kazakh patients in Xinjiang

et al. 2019

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“…Although icterus resolved in our patients, USP53 disease appears unlikely to be entirely bland; light microscopy of liver biopsy material found, along with intralobular cholestasis, fibrosis with parenchymal nodularity (cirrhotic transformation) in four patients aged ≈ 10 months (P3, P4, P6 and P7). Severe TJP2 disease predisposes to hepatocellular malignancy 21,22 . Monitoring of USP53 ‐disease patients for malignancy may be in order.…”

Section: Discussionmentioning

confidence: 99%

Low‐GGT intrahepatic cholestasis associated with biallelic USP53 variants: Clinical, histological and ultrastructural characterization

Zhang

Yong

Gong

et al. 2020

Liver International

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Background & Aims:In about 20% of children with cholestasis and normal or low serum gamma-glutamyltransferase (GGT) activity, no aetiology is identified. We sought new genes implicated in paediatric hepatobiliary disease. Methods:We conducted whole-exome sequencing in 69 children evaluated at our centre from 2011 to 2018 who had low-GGT cholestasis and in whom homozygous/ compound heterozygous predictedly pathogenic variants (PPVs) in ATP8B1, ABCB11, NR1H4, MYO5B or TJP2 were not found. Clinical records and findings on light microscopy and transmission electron microscopy of liver biopsy materials were reviewed. Results:In seven patients from seven unrelated families, biallelic PPVs (10 in total) were found in USP53, recently associated with intrahepatic cholestasis. Seven variants were classified as pathogenic: one canonical splicing, c.

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“…Among those 12 children, 9 have required liver transplantation, 2 had stable liver disease with mild portal hypertension, 1 had recurrent unexplained hematomas, and 1 had poorly characterized lung disease [6]. Three reported pediatric HCC cases with TJP2 mutations (1homozygosity of c.817delG, 1 compound heterozygous mutations of c.2668-1G > T/c.2438dupT, and 1 homozygous deletion of exon 18) were affected by very early onset of jaundice with normal range of GGT, 2 have required liver transplantation, and 1 was dead [15, 16]. Differently with pediatric TJP2 deficiency cases, several late onset adult patients with TJP2 heterozygous mutations presented high level of GGT [17].…”

Section: Discussionmentioning

confidence: 99%

Novel compound heterozygote mutations of TJP2 in a Chinese child with progressive cholestatic liver disease

Zhang

Xiao

et al. 2019

BMC Med Genet

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BackgroundProgressive familial intrahepatic cholestasis (PFIC) is a group of genetic autosomal recessive disorders that predominantly affects young children and results in early-onset progressive liver damage. Several types of PFIC were defined based on different genetic aetiologies in last decades.Case presentationHere, we report a Chinese young child diagnosed as PFIC with variants in tight junction protein 2 (TJP2). The patient was affected by a long history of jaundice, pruritus, and failure to thrive. Highly elevated level of serum total bile acid (TBA) and normal levels of gamma-glutamyltransferase (GGT) were observed at hospitalization. The patient’s clinical symptoms could be alleviated by administration of ursodeoxycholic acid. Genetic testing by next generation sequencing (NGS) found novel compound heterozygote mutations c.2448 + 1G > C/c.2639delC (p.T880Sfs*12) in TJP2, which were inherited from her mother and father, respectively. Both mutations were predicted to abolish TJP2 protein translation, and neither has previously been identified.ConclusionWe report a Chinese female PFIC child with novel compound heterozygous mutations of TJP2. Genetic testing by NGS is valuable in the clinical diagnosis of hereditary liver disease.Electronic supplementary materialThe online version of this article (10.1186/s12881-019-0753-7) contains supplementary material, which is available to authorized users.

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Paediatric hepatocellular carcinoma in tight junction protein 2 (TJP2) deficiency

Cited by 35 publications

References 19 publications

Identifying the differentially expressed microRNAs in esophagus squamous cell carcinoma of Kazakh patients in Xinjiang

Identifying the differentially expressed microRNAs in esophagus squamous cell carcinoma of Kazakh patients in Xinjiang

Low‐GGT intrahepatic cholestasis associated with biallelic USP53 variants: Clinical, histological and ultrastructural characterization

Novel compound heterozygote mutations of TJP2 in a Chinese child with progressive cholestatic liver disease

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