Abstract:
OBJECTIVE:We aimed at the identification of genetic alterations that may functionally substitute for CTNNB1 mutation in ß-catenin-activated hepatocellular adenomas (HCAs) and hepatocellular carcinoma (HCC). DESIGN:Large cohorts of HCA (n=185) and HCC (n=468) were classified using immunohistochemistry. The mutational status of the CTNNB1 gene was determined in ß-catenin-activated HCA (b-HCA) and HCC with at least moderate nuclear CTNNB1 accumulation. Ultra-deep sequencing was used to characterise CTNNB1wild-type and ß-catenin-activated HCA and HCC. Expression profiling of HCA subtypes was performed. RESULTS:A roof plate-specific spondin 2 (RSPO2) gene rearrangement resulting from a 46.4 kb microdeletion on chromosome 8q23.1 was detected as a new morphomolecular driver of β-catenin-activated HCA. RSPO2 fusion positive HCA displayed upregulation of RSPO2 protein, nuclear accumulation of β-catenin and transcriptional activation of β-catenin-target genes indicating activation of Wingless-Type MMTV Integration Site Family (WNT) signalling. Architectural and cytological atypia as well as interstitial invasion indicated malignant transformation in one of the RSPO2 rearranged b-HCAs. The RSPO2 gene rearrangement was also observed in three β-catenin-activated HCCs developing in context of chronic liver disease. Mutations of the human telomerase reverse transcriptase promoter-known to drive malignant transformation of CTNNB1-mutated HCA-seem to be dispensable for RSPO2 rearranged HCA and HCC. CONCLUSION:The RSPO2 gene rearrangement leads to oncogenic activation of the WNT signalling pathway in HCA and HCC, represents an alternative mechanism for the development of b-HCA and may drive malignant transformation without additional TERT promoter mutation.
journal_name
Gutjournal_title
Gutauthors
Longerich T,Endris V,Neumann O,Rempel E,Kirchner M,Abadi Z,Uhrig S,Kriegsmann M,Weiss KH,Breuhahn K,Mehrabi A,Weber TF,Wilkens L,Straub BK,Rosenwald A,Schulze F,Brors B,Froehling S,Pellegrino R,Budczies J,Schirmacdoi
10.1136/gutjnl-2018-317632subject
Has Abstractpub_date
2019-07-01 00:00:00pages
1287-1296issue
7eissn
0017-5749issn
1468-3288pii
gutjnl-2018-317632journal_volume
68pub_type
杂志文章相关文献
GUT文献大全abstract:OBJECTIVES:No trial has compared non-bismuth quadruple 'sequential' and 'concomitant' regimens in settings with increasing clarithromycin rates. The study aims to compare the effectiveness and safety of these therapies for Helicobacter pylori treatment. DESIGN:Prospective randomised clinical trial in 11 Spanish hospit...
journal_title:Gut
pub_type: 杂志文章,随机对照试验
doi:10.1136/gutjnl-2013-304820
更新日期:2014-02-01 00:00:00
abstract::Family histories were obtained from 50 patients with adenocarcinoma of the colon or rectum in north-east Scotland. A comparable control group was similarly interviewed and in each group the case notes of the first degree relatives were studied where possible. Eight (16%) of the patients with cancer of the colon or rec...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.23.2.169
更新日期:1982-02-01 00:00:00
abstract::Both carbachol (10(-4)-10(-3) mol/l) and cholecystokinin octapeptide (CCK-8) (10(-8)-10(-6) mol/l) significantly stimulated the release of pepsinogen from rabbit gastric mucosa maintained in organ culture (213-216% and 143-261% of control, respectively, p less than 0.05-0.01). The secretion was not affected by removin...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.33.1.21
更新日期:1992-01-01 00:00:00
abstract:BACKGROUND AND AIMS:The authors have previously isolated a putative oncogene, eukaryotic initiation factor 5A2 (EIF5A2) from 3q26. In this study, EIF5A2 was characterised for its role in colorectal carcinoma (CRC) aggressiveness and underlying molecular mechanisms. METHODS:The expression dynamics of EIF5A2 were examin...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gutjnl-2011-300207
更新日期:2012-04-01 00:00:00
abstract:OBJECTIVES:Recent studies using the lactulose hydrogen breath test (LHBT) suggest most patients with irritable bowel syndrome (IBS) have small intestinal bacterial overgrowth (SIBO). However, the validity of the LHBT has been questioned, particularly as this test could reflect changes in oro-caecal transit. Therefore, ...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.2009.205476
更新日期:2011-03-01 00:00:00
abstract::Recent evidence suggests that the production of colorectal carcinogens is facilitated when the pH of the colonic contents is alkaline. It follows that the colonic intraluminal pH of patients with colorectal neoplasms should be higher than in normal subjects. Gastrointestinal pH has been measured in 30 patients with co...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.31.12.1355
更新日期:1990-12-01 00:00:00
abstract:BACKGROUND:It has been suggested that slow transit constipation (STC) may be part of a panenteric motor disorder. AIM:To evaluate motility of an upper gastrointestinal organ, the gall bladder, in 16 patients with STC and 20 healthy controls. METHODS:Gall bladder emptying (ultrasonography) was studied in response to n...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.45.2.264
更新日期:1999-08-01 00:00:00
abstract:BACKGROUND:The intestinal epithelium is covered by a continuous layer of mucus which is secreted by well differentiated epithelial cells. Disregulation of the expression of mucins has been reported to have possible implications in the neoplastic process which affects intestinal mucosae. It is well known that preneoplas...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.43.4.519
更新日期:1998-10-01 00:00:00
abstract::Intestinal protein loss in chronic inflammatory bowel diseases may be easily determined by measurement of alpha-1-antitrypsin (alpha 1-AT) stool concentration and alpha 1-AT clearance. Both parameters were significantly raised in 36 and 34 patients respectively with chronic inflammatory bowel diseases, compared with e...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.28.4.386
更新日期:1987-04-01 00:00:00
abstract:BACKGROUND AND AIMS:Bariatric surgery is increasingly performed worldwide to treat morbid obesity and is also known as metabolic surgery to reflect its beneficial metabolic effects especially with respect to improvement in type 2 diabetes. Understanding surgical weight loss mechanisms and metabolic modulation is requir...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.2010.234708
更新日期:2011-09-01 00:00:00
abstract:BACKGROUND:The long-term performance of colorectal cancer (CRC) screening programmes based on a 2-year faecal immunochemical test (FIT) is still unclear. METHODS:In a sample of 50 to 69-year-olds repeatedly screened with the FIT (OC-Hemodia latex agglutination test; cut-off: 20 µg haemoglobin/g faeces), we examined: (...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gutjnl-2017-314753
更新日期:2018-12-01 00:00:00
abstract:BACKGROUND:Most direct understanding of enteric nerve (patho)physiology has been obtained by electrode and imaging techniques in animal models and human surgical samples. Until now, neuronal activity recordings from a more accessible human tissue source have remained a true challenge. OBJECTIVES:To record nerve activi...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gutjnl-2011-301777
更新日期:2013-02-01 00:00:00
abstract:BACKGROUND:Nitric oxide is a major neurotransmitter in non-adrenergic, non-cholinergic (NANC) pathways. NANC inhibitory innervation has been shown in human gall bladder muscle in vitro; the role of nitric oxide in human gall bladder emptying however is undefined. AIMS:To study the effect of glyceryl trinitrate, a nitr...
journal_title:Gut
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1136/gut.42.3.410
更新日期:1998-03-01 00:00:00
abstract:BACKGROUND:Recent reports have described a modulating influence of nitric oxide (NO) on intestinal mucosal permeability and have implicated a role for mast cells in this NO mediated process. AIMS:To assess further the contribution of mast cells to the mucosal permeability changes elicited by the NO synthase (NOS) inhi...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.41.5.636
更新日期:1997-11-01 00:00:00
abstract::Five cases of volvulus of varying lengths of the small intestine are described. The incidence and the aetiology of the condition are briefly discussed. Shock as a feature of extensive volvulus is stressed, and its cause in these cases is related to the previous animal experimental work of others. The other clinical fe...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.1.1.76
更新日期:1960-03-01 00:00:00
abstract:AIMS:To compare jejunal mucosal morphometry in HIV infected patients resident in London and Uganda. PATIENTS:Twenty HIV positive patients from London and 16 from Uganda were studied, and compared with HIV negative control subjects from both sites. METHODS:Stools and biopsy specimens were examined for enteropathogens....
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.43.3.350
更新日期:1998-09-01 00:00:00
abstract::Forty patients with endoscopically proven persistent duodenal ulcer who had been treated for six weeks with cimetidine (1 g/day) were randomly allocated to receive a further six weeks' treatment with cimetidine (1 g/day) or ranitidine (300 mg/day). Ulcers healed in 12 of 19 patients given cimetidine (63%) and in 13 of...
journal_title:Gut
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1136/gut.25.10.1113
更新日期:1984-10-01 00:00:00
abstract:BACKGROUND:IgA class serum autoantibodies against type 2 (tissue) transglutaminase (TG2) bind to both intestinal and extraintestinal normal tissue sections in vitro, eliciting endomysial, reticulin, and jejunal antibody reactions. It is not known whether similar binding also occurs in coeliac patients in vivo, and may ...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.2003.024836
更新日期:2004-05-01 00:00:00
abstract::Endoscopic sphincterotomy has become the first line treatment for patients with common bile duct (CBD) stones. This technique may fail, however, due to difficult anatomy, previous surgery, periampullary diverticula or the presence of a large stone. The importance of stone size to the success of endoscopic sphincteroto...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.34.12.1718
更新日期:1993-12-01 00:00:00
abstract:OBJECTIVES:To compare performance measures across all three rounds of the English bowel cancer screening faecal occult blood test pilot and their relation to social deprivation and ethnicity. METHODS:In each round in three primary care trusts, data for a restricted population of over 48,500 aged 60-69 years were analy...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.2010.236430
更新日期:2012-01-01 00:00:00
abstract::Faecal chymotrypsin was measured in patients with chronic pancreatitis and in healthy black urban and rural control subjects. In the patients, significantly lower values of faecal chymotrypsin were obtained (mean (SD) 2.4 1.79 U/g stool) whereas in urban control subjects, values were within the normal range (mean (SD)...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.32.3.321
更新日期:1991-03-01 00:00:00
abstract:BACKGROUND:Patients with Crohn's disease suffer from intestinal bile acid malabsorption. Intestinal bile acid absorption is mediated by the apical sodium dependent bile acid transporter ASBT/IBAT (SLC10A2). In rats, ASBT is induced by glucocorticoids. AIMS:To study whether human ASBT is activated by glucocorticoids an...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.53.1.78
更新日期:2004-01-01 00:00:00
abstract::Two peptides which are potent stimulants of gastric acid secretion are isolated from Zollinger-Ellison tumour tissue. They have aminoacid constitutions identical with those of human gastrin types I and II as isolated from human antral mucosa, and they are present in similar proportions. Their electrophoretic and chrom...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.10.8.603
更新日期:1969-08-01 00:00:00
abstract::The effect of octreotide, a synthetic analogue of somatostatin, on the modulation of the acetic acid model of experimental colitis was examined. Colitis was induced by intracolonic administration of 2 ml of 5% acetic acid. The inflammatory response elicited by the acetic acid resulted in increased colonic synthesis of...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.34.2.264
更新日期:1993-02-01 00:00:00
abstract::In a single centre double blind study of 66 patients, the value of cisapride (10 mg twice daily) was compared with placebo in the prevention of duodenal ulcer relapse. Patients who remained ulcer free attended for clinical review every two months and had a mandatory endoscopy at 0, 4, 8, and 12 months or if symptoms s...
journal_title:Gut
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1136/gut.34.8.1042
更新日期:1993-08-01 00:00:00
abstract:BACKGROUND:Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit cyclooxygenase (COX) and cause gastric ulceration. NSAIDs also impair granulation tissue angiogenesis and healing of established gastric ulcers in humans. The mechanism whereby NSAIDs inhibit granulation tissue angiogenesis is unknown but may involve inh...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.45.4.529
更新日期:1999-10-01 00:00:00
abstract:OBJECTIVE:The aim of the study was to compare azathioprine versus mesalazine tablets for the prevention of clinical recurrence in patients with postoperative Crohn's disease (CD) with moderate or severe endoscopic recurrence. METHODS:This was a 1 year, double-blind, double-dummy, randomised study which took place in 2...
journal_title:Gut
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1136/gut.2009.194159
更新日期:2010-06-01 00:00:00
abstract:BACKGROUND:Eradication of Barrett's mucosa by thermal or photoablation combined with high doses of proton pump inhibitors is a potentially attractive strategy in the management of this preneoplastic condition. However, major concerns of this method are the persistence of residual metaplastic glands beneath the new squa...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.46.4.574
更新日期:2000-04-01 00:00:00
abstract::Lymphangiomas are rare tumours of lymphatic vessels, most commonly found in children. We present the unusual case of small bowel obstruction caused by benign lymphangioma in a middle aged woman. ...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.32.12.1568
更新日期:1991-12-01 00:00:00
abstract::The lectin, phytohaemagglutinin, present in beans survives passage through the gastrointestinal tract in a biologically and immunologically intact form. It is known that by binding to the brush border membranes of the small intestine phytohaemagglutinin induces its hyperplastic growth. However, its effect on the other...
journal_title:Gut
pub_type: 杂志文章
doi:10.1136/gut.37.3.353
更新日期:1995-09-01 00:00:00