Early-onset hepatocellular carcinoma (HCC) accounts for 15%-20% of total HCC cases in Asia, and the incidence is increasing. The low frequency of cirrhosis and poor prognosis of early-onset HCC suggests that its mechanisms may differ from late-onset HCC. Although hepatitis B virus (HBV) infection is epidemiologically associated with HCC, the role of HBV in early-onset HCC remains poorly understood. Here, we report a comparative study of HBV subgenotypes and integration in early-( £ 30) and late-onset (70) HBV-associated HCC using a novel high-throughput viral integration detection method. We report that HBV B2 is predominantly present in early-onset HCC. HBV integration is a common phenomenon, both in early-and late-onset HCC, which favors integrating into human repeat regions. Moreover, we found a breakpoint in 8q24 located between c-Myc and plasmocytoma variant translocation 1 (PVT1), which was detected in 12.4% (14 of 113) of early-onset HCCs, but only 1.4% (2 of 145) in lateonset HCCs. HBV integrating this site results in c-MYC, PVT1, and microRNA-1204 overexpression in tumors, thereby potentially contributing to the development of earlyonset HCC. Conclusion: HBV genotype and integration patterns may be distinct in early-onset HCC. Our results may shed light on HCC risk factors in young HBV carriers. Further studies are needed to elucidate at which time in tumor development this integration event occurs and whether it plays an important, causative role in HCC development or progression. (HEPATOLOGY 2015;61:1821-1831 H epatocellular carcinoma (HCC) is a common solid tumor and the third leading cause of cancer death worldwide.1 Hepatitis B virus (HBV) is a major etiological agent in China, Southeast Asia, and sub-Saharan Africa, and individuals with chronic HBV infection are at increased risk of developing HCC, particularly those with chronic liver disease and cirrhosis.2 Average age at onset of HBVassociated HCC is 50 years 3,4 ; thus, the recommendations advise HCC screening for Asian male HBV patients older than 40 and Asian female HBV patients older than 50.5 Nonetheless, incidence of HCC in patients younger than 40, especially in high-risk populations, is relatively high. 6,7 Recent studies have reported a significant prevalence and worse prognosis in early-onset HCC patients, 8,9 suggesting that there Abbreviations: ALB, albumin; bp, base pairs; DR1/2, direct repeat 1 and 2; FN1, fibronectin 1; GATM, glycine amidinotransferase; gDNA, genomic DNA; HBV, hepatitis B virus; Hbx, HBV x gene; HCC, hepatocellular carcinoma; HIVID, high-throughput viral integration detection; kb, kilobase; LC, liver cirrhosis; LINE, long interspersed nuclear elements; miR, microRNA; MLL4, myeloid/lymphoid or mixed-lineage leukemia 4; PVT1, plasmocytoma variant translocation 1; RT-PCR, reverse-transcription polymerase chain reaction; SINE, short interspersed nuclear elements; ST18, suppression of tumorigenicity 18; STAT1, signal transducer and activator of transcription 1; SYT12, synaptotagmin XII; TERT, telomerase reverse transc...

No abstract

BackgroundPeutz-Jeghers syndrome (PJS) is caused by mutations in serine/threonine kinase 11 (STK11) gene. The increased cancer risk has been connected to P53 pathway.MethodsPJS probands with STK11 mutation were included in the function analysis. P53 activity elevated by STK11 mutants was investigated using dual-luciferase reporter assay in vitro after constructing expression vectors of STK11 wild type and mutants generated by site-directed substitution. The association between the P53 activity and clinicopathological factors was analysis, especially the cancer history.ResultsThirteen probands with STK11 mutations were involved, and within the mutations, c.G924A was novel. P53 activity elevation caused by 6 truncating mutations were significantly lower than that of STK11 wild type (P < 0.05). Family history of cancer was observed in 5 families. Within them, P53 activity was reduced and cancer occurred before 40 in 2 families, while it was not significantly changed and cancers happened after 45 in the other 3 families.ConclusionsThe affected P53 activity caused by STK11 mutations in PJS patients is significantly associated with protein truncation, while cancer risk in PJS can be elevated through pathways rather than P53 pathway. P53 activity test is probably a useful supporting method to predict cancer risk in PJS, which could be helpful in clinical practice.Electronic supplementary materialThe online version of this article (10.1186/s12881-018-0626-5) contains supplementary material, which is available to authorized users.

An enzyme-linked immunosorbent assay (ELISA) using antigenic |Vgalactosidasc-D/ra///aria immilis recombinant fusion protein (FP) obtained by the recombinant DNA technique provided a useful diagnostic tool for human dirofilariasis. D. immitis-tnteclcd human sera reacted strongly with FP that was immobilized with anti-(3-galactosidase monoclonal antibody on microplates. However, the FP did not react with sera from patients with other filariasis. In detection of anti-D. immitis IgG antibody, ELISA using FP was highly sensitive and specific compared to that using crude somatic antigen.

BackgroundPeutz-Jeghers syndrome (PJS) is caused by mutations in the tumor suppressor gene, STK11, and is characterized by gastrointestinal hamartomas, melanin spots on the lips and the extremities, and an increased risk of developing cancer.Case presentationWe reported an isolated PJS patient who died of colon cancer, whose blood sample was collected together with all the available family members’. The entire coding region of the STK11 gene was amplified by PCR and analyzed by Sanger sequencing, through which, a novel mutation, c.962_963delCC in exon 8 was identified in this patient. This mutation causes a frameshift mutation and a premature termination at codon 358. Protein structure prediction by Swiss-Model indicated a dramatic change and partial loss of the C-terminal domain. We did not observe this mutation in both parents of the proband. Therefore, it is considered a novel de-novo mutation. Furthermore, the mutation was not found in 50 unrelated healthy people.ConclusionsThe novel mutation we reported here had not been recorded in databases or literature, and the patient who possessed it suffered from PJS and colon cancer. So our results enlarge the spectrum of STK11 variants in PJS patients. This mutation is most likely responsible for development of the PJS phenotype, especially the cancer occurrence.Electronic supplementary materialThe online version of this article (10.1186/s12881-017-0471-y) contains supplementary material, which is available to authorized users.