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Exome and genome sequencing of nasopharynx cancer identifies NF-κB pathway activating mutations

Li, Yvonne Y ; Chung, Grace T. Y. ; Lui, Vivian W. Y. ; [et al.]

Springer Science and Business Media LLC ; 2017

In: Nature Communications Vol. 8, No. 1 ( 2017-01-18)

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In: Nature Communications, Springer Science and Business Media LLC, Vol. 8, No. 1 ( 2017-01-18)

Abstract: Nasopharyngeal carcinoma (NPC) is an aggressive head and neck cancer characterized by Epstein-Barr virus (EBV) infection and dense lymphocyte infiltration. The scarcity of NPC genomic data hinders the understanding of NPC biology, disease progression and rational therapy design. Here we performed whole-exome sequencing (WES) on 111 micro-dissected EBV-positive NPCs, with 15 cases subjected to further whole-genome sequencing (WGS), to determine its mutational landscape. We identified enrichment for genomic aberrations of multiple negative regulators of the NF-κB pathway, including CYLD , TRAF 3, NFKBIA and NLRC5, in a total of 41% of cases. Functional analysis confirmed inactivating CYLD mutations as drivers for NPC cell growth. The EBV oncoprotein latent membrane protein 1 (LMP1) functions to constitutively activate NF-κB signalling, and we observed mutual exclusivity among tumours with somatic NF-κB pathway aberrations and LMP1-overexpression, suggesting that NF-κB activation is selected for by both somatic and viral events during NPC pathogenesis.

Type of Medium: Online Resource

ISSN: 2041-1723

URL: Article

DOI: 10.1038/ncomms14121

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2017

detail.hit.zdb_id: 2553671-0

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Clinical utility of plasma Epstein‐Barr virus DNA and ERCC1 single nucleotide polymorphism in nasopharyngeal carcinoma

Hui, Edwin P. ; Ma, Brigette B. Y. ; Chan, K. C. Allen ; [et al.]

Wiley ; 2015

In: Cancer Vol. 121, No. 16 ( 2015-08-15), p. 2720-2729

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In: Cancer, Wiley, Vol. 121, No. 16 ( 2015-08-15), p. 2720-2729

Abstract: In a prospective biomarker study of patients with nasopharyngeal cancer, plasma Epstein‐Barr virus DNA is validated as the most significant prognostic biomarker for use in selecting high‐risk patients for adjuvant therapy. The ERCC1 C118T genotype may help to identify a favorable subgroup of patients (approximately 7%) with plasma Epstein‐Barr virus DNA‐negative nasopharyngeal cancer who have an excellent prognosis and can be spared the toxicities of further therapy.

Type of Medium: Online Resource

ISSN: 0008-543X , 1097-0142

URL: Issue

URL: Article

DOI: 10.1002/cncr.v121.16

DOI: 10.1002/cncr.29413

Language: English

Publisher: Wiley

Publication Date: 2015

detail.hit.zdb_id: 1479932-7

detail.hit.zdb_id: 2599218-1

detail.hit.zdb_id: 2594979-2

detail.hit.zdb_id: 1429-1

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DNA of Erythroid Origin Is Present in Human Plasma and Informs the Types of Anemia

Lam, W K Jacky ; Gai, Wanxia ; Sun, Kun ; [et al.]

Oxford University Press (OUP) ; 2017

In: Clinical Chemistry Vol. 63, No. 10 ( 2017-10-01), p. 1614-1623

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In: Clinical Chemistry, Oxford University Press (OUP), Vol. 63, No. 10 ( 2017-10-01), p. 1614-1623

Abstract: There is much interest in the tissue of origin of circulating DNA in plasma. Data generated using DNA methylation markers have suggested that hematopoietic cells of white cell lineages are important contributors to the circulating DNA pool. However, it is not known whether cells of the erythroid lineage would also release DNA into the plasma. METHODS Using high-resolution methylation profiles of erythroblasts and other tissue types, 3 genomic loci were found to be hypomethylated in erythroblasts but hypermethylated in other cell types. We developed digital PCR assays for measuring erythroid DNA using the differentially methylated region for each locus. RESULTS Based on the methylation marker in the ferrochelatase gene, erythroid DNA represented a median of 30.1% of the plasma DNA of healthy subjects. In subjects with anemia of different etiologies, quantitative analysis of circulating erythroid DNA could reflect the erythropoietic activity in the bone marrow. For patients with reduced erythropoietic activity, as exemplified by aplastic anemia, the percentage of circulating erythroid DNA was decreased. For patients with increased but ineffective erythropoiesis, as exemplified by β-thalassemia major, the percentage was increased. In addition, the plasma concentration of erythroid DNA was found to correlate with treatment response in aplastic anemia and iron deficiency anemia. Plasma DNA analysis using digital PCR assays targeting the other 2 differentially methylated regions showed similar findings. CONCLUSIONS Erythroid DNA is a hitherto unrecognized major component of the circulating DNA pool and is a noninvasive biomarker for differential diagnosis and monitoring of anemia.

Type of Medium: Online Resource

ISSN: 0009-9147 , 1530-8561

URL: Article

DOI: 10.1373/clinchem.2017.272401

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2017

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Liver- and Colon-Specific DNA Methylation Markers in Plasma for Investigation of Colorectal Cancers with or without Liver Metastases

Gai, Wanxia ; Ji, Lu ; Lam, W K Jacky ; [et al.]

Oxford University Press (OUP) ; 2018

In: Clinical Chemistry Vol. 64, No. 8 ( 2018-08-01), p. 1239-1249

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In: Clinical Chemistry, Oxford University Press (OUP), Vol. 64, No. 8 ( 2018-08-01), p. 1239-1249

Abstract: Measurement of DNA derived from different tissues in the circulating DNA pool can provide important information regarding the presence of many pathological conditions. However, existing methods involving genome-wide bisulfite sequencing are relatively expensive and may present challenges for large-scale analysis. METHODS Through identifying differentially methylated regions in the liver and colon compared with other tissues, we identified 2 markers and developed corresponding droplet digital PCR assays. Plasma concentrations of liver-derived and colon-derived DNA were measured for 13 liver transplant recipients, 40 liver cancer patients, and 62 colorectal cancer (CRC) patients (27 with and 35 without liver metastases). RESULTS In liver transplant recipients, the fractional concentration of liver-derived DNA measured using the liver-specific methylation marker and donor-specific alleles showed good correlation (Pearson R = 0.99). In liver cancer patients, the concentration of liver-derived DNA correlated positively with the maximal dimension of the tumor (Spearman R = 0.74). In CRC patients with and without liver metastasis, the plasma concentrations of colon-derived DNA (median, 138 copies/mL and 4 copies/mL, respectively) were increased compared with the 30 healthy controls (26 had undetectable concentrations). The absolute concentration of liver-derived DNA provided a better differentiation between CRC patients with and without liver metastasis compared with the fractional concentration (area under ROC curve, 0.85 vs 0.75). CONCLUSIONS Quantitative analysis of plasma DNA with tissue-specific methylation patterns using droplet digital PCR is applicable for the investigation of cancers and assessing organ transplantation. This approach is useful for differentiating patients with and without metastases to other organs.

Type of Medium: Online Resource

ISSN: 0009-9147 , 1530-8561

URL: Article

DOI: 10.1373/clinchem.2018.290304

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2018

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Non-alcoholic fatty liver disease: Spectral patterns observed from an in vivo phosphorus magnetic resonance spectroscopy study

Abrigo, Jill M. ; Shen, Jiayun ; Wong, Vincent W.-S. ; [et al.]

Elsevier BV ; 2014

In: Journal of Hepatology Vol. 60, No. 4 ( 2014-04), p. 809-815

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In: Journal of Hepatology, Elsevier BV, Vol. 60, No. 4 ( 2014-04), p. 809-815

Type of Medium: Online Resource

ISSN: 0168-8278

URL: Article

DOI: 10.1016/j.jhep.2013.11.018

Language: English

Publisher: Elsevier BV

Publication Date: 2014

detail.hit.zdb_id: 2027112-8

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Pearls of experience for safe and efficient hospital practices in otorhinolaryngology—head and neck surgery in Hong Kong during the 2019 novel coronavirus disease (COVID-19) pandemic

Cho, Ryan H. W. ; Yeung, Zenon W. C. ; Ho, Osan Y. M. ; [et al.]

Springer Science and Business Media LLC ; 2020

In: Journal of Otolaryngology - Head & Neck Surgery Vol. 49, No. 1 ( 2020-12)

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In: Journal of Otolaryngology - Head & Neck Surgery, Springer Science and Business Media LLC, Vol. 49, No. 1 ( 2020-12)

Abstract: The 2019 novel coronavirus disease (COVID-19) epidemic originated in Wuhan, China and spread rapidly worldwide, leading the World Health Organization to declare an official global COVID-19 pandemic in March 2020. In Hong Kong, clinicians and other healthcare personnel collaborated closely to combat the outbreak of COVID-19 and minimize the cross-transmission of disease among hospital staff members. In the field of otorhinolaryngology—head and neck surgery (OHNS) and its various subspecialties, contingency plans were required for patient bookings in outpatient clinics, surgeries in operating rooms, protocols in wards and other services. Infected patients may shed severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) particles into their environments via body secretions. Therefore, otolaryngologists and other healthcare personnel in this specialty face a high risk of contracting COVID-19 and must remain vigilant when performing examinations and procedures involving the nose and throat. In this article, we share our experiences of the planning and logistics undertaken to provide safe and efficient OHNS practices over the last 2 months, during the COVID-19 pandemic. We hope that our experiences will serve as pearls for otolaryngologists and other healthcare personnel working in institutes that serve large numbers of patients every day, particularly with regard to the sharing of clinical and administrative tasks during the COVID-19 pandemic.

Type of Medium: Online Resource

ISSN: 1916-0216

URL: Article

DOI: 10.1186/s40463-020-00427-4

Language: English

Publisher: Springer Science and Business Media LLC

Publication Date: 2020

detail.hit.zdb_id: 2436698-5

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Concurrent fatty liver increases risk of hepatocellular carcinoma among patients with chronic hepatitis B

Chan, Anthony W H ; Wong, Grace L H ; Chan, Hoi‐Yun ; [et al.]

Wiley ; 2017

In: Journal of Gastroenterology and Hepatology Vol. 32, No. 3 ( 2017-03), p. 667-676

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In: Journal of Gastroenterology and Hepatology, Wiley, Vol. 32, No. 3 ( 2017-03), p. 667-676

Abstract: Concurrent fatty liver in hepatitis B virus (HBV)‐infected patients without significant alcohol intake is a frequent and increasingly alarming problem because of the non‐alcoholic fatty liver disease pandemic. The risk of HBV‐related hepatocellular carcinoma (HCC) development was increased by concomitant obesity and diabetes. Direct evidence of the hepatocarcinogenic effect of fatty liver in chronic HBV remains elusive. We aimed to evaluate the risk of concurrent histologically proven fatty liver in HBV hepatocarcinogenesis. Methods We conducted a retrospective cohort study on a liver biopsy cohort of HBV‐infected patients without significant alcohol intake to evaluate the prevalence of concurrent histologically proven fatty liver and its association with subsequent HCC development. We also examined nine polymorphisms on six non‐alcoholic fatty liver disease‐related candidate genes ( ADIPOQ , APOC3 , GCKR , LEPR , PNPLA3 , and PPARG ). Results Among 270 HBV‐infected patients, concurrent fatty liver was found in 107 patients (39.6%) and was associated with metabolic risks, cirrhosis ( P = 0.016) and PNPLA3 rs738409 CG/GG genotype ( P = 0.002). At a median follow‐up of 79.9 months, 11 patients (4.1%) developed HCC, and nine of them had concurrent fatty liver. By multivariable Cox analysis, concurrent fatty liver (HR 7.27, 95% confidence interval: 1.52–34.76; P = 0.013), age, cirrhosis, and APOC3 rs2854116 TC/CC genotype (HR 3.93, 95% confidence interval: 1.30–11.84; P = 0.013) were independent factors predicting HCC development. Conclusions Concurrent fatty liver is common in HBV‐infected patients and an independent risk factor potentiating HBV‐associated HCC development by 7.3‐fold. The risk of HBV‐related HCC is increased by APOC3 gene polymorphism, and further characterization is required by its role.

Type of Medium: Online Resource

ISSN: 0815-9319 , 1440-1746

URL: Issue

URL: Article

DOI: 10.1111/jgh.2017.32.issue-3

DOI: 10.1111/jgh.13536

Language: English

Publisher: Wiley

Publication Date: 2017

detail.hit.zdb_id: 2006782-3

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Dysregulated Lysine Acetyltransferase 2B Promotes Inflammatory Bowel Disease Pathogenesis Through Transcriptional Repression of Interleukin-10

Bai, Alfa H. C. ; Wu, William K. K. ; Xu, Liangliang ; [et al.]

Oxford University Press (OUP) ; 2016

In: Journal of Crohn's and Colitis Vol. 10, No. 6 ( 2016-06), p. 726-734

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In: Journal of Crohn's and Colitis, Oxford University Press (OUP), Vol. 10, No. 6 ( 2016-06), p. 726-734

Type of Medium: Online Resource

ISSN: 1873-9946 , 1876-4479

URL: Article

DOI: 10.1093/ecco-jcc/jjw020

Language: English

Publisher: Oxford University Press (OUP)

Publication Date: 2016

detail.hit.zdb_id: 2389631-0

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Receptor tyrosine kinase fusions act as a significant alternative driver of the serrated pathway in colorectal cancer development

Chan, Anthony W‐H ; Pan, Yi ; Tong, Joanna H‐M ; [et al.]

Wiley ; 2020

In: The Journal of Pathology Vol. 251, No. 1 ( 2020-05), p. 74-86

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In: The Journal of Pathology, Wiley, Vol. 251, No. 1 ( 2020-05), p. 74-86

Abstract: Serrated polyps are a clinically and molecularly heterogeneous group of lesions that can contribute to the development of colorectal cancers (CRCs). However, the molecular mechanism underlying the development of serrated lesions is still not well understood. Here, we combined multiple approaches to analyze the genetic alterations in 86 colorectal adenomas (including 35 sessile serrated lesions, 15 traditional adenomas, and 36 conventional adenomatous polyps). We also investigated the in vitro and in vivo oncogenic properties of a novel variant of the NCOA4–RET fusion gene. Molecular profiling revealed that sessile serrated lesions and traditional serrated adenomas have distinct clinicopathological and molecular features. Moreover, we identified receptor tyrosine kinase translocations exclusively in sessile serrated lesions (17%), and the observation was validated in a separate cohort of 34 sessile serrated lesions (15%). The kinase fusions as well as the BRAF and KRAS mutations were mutually exclusive to each other. Ectopic expression of a novel variant of the NCOA4–RET fusion gene promoted cell proliferation in vitro and in vivo , and the proliferation was significantly suppressed by RET kinase inhibitors. All of these underscored the importance of mitogen‐activated protein kinase (MAPK) pathway activation in the serrated pathway of colorectal tumorigenesis. In addition, we demonstrated that the kinase fusion may occur early in the precursor lesion and subsequent loss of TP53 may drives the transformation to carcinoma during serrated tumorigenesis. In conclusion, we identified kinase fusions as a significant alternative driver of the serrated pathway in colorectal cancer development, and detecting their presence may serve as a biomarker for the diagnosis of sessile serrated lesions. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Type of Medium: Online Resource

ISSN: 0022-3417 , 1096-9896

URL: Issue

URL: Article

DOI: 10.1002/path.v251.1

DOI: 10.1002/path.5418

RVK:

XA 10000

Language: English

Publisher: Wiley

Publication Date: 2020

detail.hit.zdb_id: 1475280-3

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Increased liver stiffness measurement by transient elastography in severe acute exacerbation of chronic hepatitis B

Wong, Grace L-H ; Wong, Vincent W-S ; Choi, Paul C-L ; [et al.]

Wiley ; 2009

In: Journal of Gastroenterology and Hepatology Vol. 24, No. 6 ( 2009-06), p. 1002-1007

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In: Journal of Gastroenterology and Hepatology, Wiley, Vol. 24, No. 6 ( 2009-06), p. 1002-1007

Type of Medium: Online Resource

ISSN: 0815-9319 , 1440-1746

URL: Issue

URL: Article

DOI: 10.1111/jgh.2009.24.issue-6

DOI: 10.1111/j.1440-1746.2009.05779.x

Language: English

Publisher: Wiley

Publication Date: 2009

detail.hit.zdb_id: 2006782-3

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