Navigation Links
New oncogene gives valuable insight into hepatocellular tumors in humans

Copenhagen, Denmark, Thursday 23 April: The first identification of GP130 somatic activating mutations* in human tumours was announced today at EASL 2009, the Annual Meeting of the European Association for the Study of Liver Disease in Copenhagen, Denmark.

Identification of recurrent somatic mutation activating GP130 in inflammatory hepatocellular tumours reveals a new pathway of tumourigenesis in humans, according to researchers. This finding reinforces the role of inflammation in hepatocarcinogenesis and particularly in the malignant transformation of hepatocellular adenomas (HCA). Moreover, GP130 mutations will enable the refinement of the molecular classification of hepatocellular tumors in humans.

Inflammatory hepatocellular adenomas (IHCA) are benign liver tumours defined by the presence of inflammatory infiltrates and by an over-expression of inflammatory proteins. IHCA are usually developed in women and their occurrence is frequently associated with obesity and alcohol intake. Recently, somatic mutations were identified that activated GP130 in 60% of IHCA (Rebouissou et al, Nature, 2009), thus defining GP130 as a new oncogene in human tumours. This study aimed to evaluate frequency of GP130 mutations in a wide series of tumours.

Dr Jessica Zucman-Rossi of Inserm U674, Paris, France, who led the study, said: "This exciting advance means we now have a novel means of further investigating the development pathway of hepatocellular tumours as well as a new tool in the classification of hepatocellular tumours. It is an important step forward in our understanding of hepatocarcinogenesis and the future management of this disease."

Researchers in this study screened a series of 400 well-characterised hepatocellular tumours including hepatocellular adenomas, carcinomas, hepatocholangio-carcinoma, fibrolamellar carcinomas and intra-hepatic cholangiocarcinomas. 100 tumours from different organs were also collected. To search for mutations, GP130 exons were screened in all samples and the function of 7 different mutants was analysed in HEP3B.

A somatic mutation was identified in 65% of the IHCA including 24 different small in-frame deletions or duplications. A spectrum of mutations shows that mutations clearly target the IL-6 binding site in GP130. Also demonstrated was the fact that the expression of the most frequent GP130 mutants in HEP3B cells activates STAT3 in absence of IL-6. The researchers searched for possible interaction and cooperation of GP130 activation with other pathways altered in hepatocellular adenoma. HNF1α inactivation and gp130 activation were mutually exclusive in HCA (P< 10-4). By contrast, in half of the -catenin activating HCA, a GP130-activating mutation was identified. For two IHCA associated with a malignant transformation, both an activating gp130 and -catenin mutations were found. Further, analysis of 220 hepatocellular carcinomas revealed rare GP130 alterations in all cases accompanied by -catenin-activating mutations, suggesting a cooperative effect of these signalling pathways in the malignant transformation of hepatocytes.


Contact: Camilla Dormer
European Association for the Study of the Liver

Related medicine news :

1. MicroRNA controls expression of oncogenes
2. Colon Cancer Oncogene Discovered
3. Blocking Oncogene Can Stop Spread of Ovarian Cancer
4. Oncogene inhibits tumor suppressor to promote cancer: Study links B-RAF and LKB1
5. Online Epidemic Gives Clues to Bird Flu Spread
6. Welch Foundation gives $1.6 million for drug discovery research
7. 24 Hour Fitness Gives The Biggest Loser High-Tech Upgrade
8. New Technology at Unitrin Direct Gives Customers an Alternative to Waiting
9. Ancient mechanism for coping with stresses also gives cancer a boost
10. What gives us sunburn protects crayfish against bacteria
11. Bellevue Dentist Gives a Thumbs Up to Britney Spears Smile
Post Your Comments:
(Date:6/27/2016)... ... June 27, 2016 , ... recently awarded their highest five-star ... , Millions of individuals in the United States and Canada wear eyeglasses. Once considered ... both correct vision and make a fashion statement. Even celebrities use glasses as a ...
(Date:6/26/2016)... ... , ... PawPaws brand pet supplements owned by Whole Health Supply ... health of felines. The formula is all-natural and is made from Chinese herbs that ... Cat Kidney Support Supplement Soft Chews are Astragalus Root Extract and Rehmannia Root ...
(Date:6/25/2016)... ... 2016 , ... Austin residents seeking Mohs surgery services, can now turn to ... Dr. Russell Peckham for medical and surgical dermatology. , Dr. Dorsey brings specialization to ... fellowship in Mohs Micrographic Surgery completed by Dr. Dorsey was under the direction of ...
(Date:6/25/2016)... , ... June 25, 2016 , ... As a lifelong ... Cum Laude and his M.D from the David Geffen School of Medicine at UCLA. ... to Los Angeles to complete his fellowship in hematology/oncology at the UCLA-Olive View-Cedars Sinai ...
(Date:6/24/2016)... ... June 24, 2016 , ... A recent article ... people are unfamiliar with. The article goes on to state that individuals are now ... of these less common operations such as calf and cheek reduction. The Los Angeles ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... Calif. , June 23, 2016 ... CST on Thursday, July 7, 2016 , , , , ... ) , , , , EXPERT PANELISTS:  , , ... Naik; Senior Industry Analyst, Christi Bird; Senior Industry Analyst, Divyaa Ravishankar ... The global pharmaceutical industry is witnessing an exceptional ...
(Date:6/23/2016)... , June 23, 2016 ... Oticon , industry leaders in advanced ... launch of Oticon Opn ™, the world,s first ... of possibilities for IoT devices.      (Photo: ... Oticon introduces a number of ,world firsts,: ...
(Date:6/23/2016)... 2016 Research and Markets has ... Global Analysis (United States, China, Japan, Brazil, United Kingdom, ... their offering. Surgical ... business planners, provides surgical procedure volume data in a ... an in-depth analysis of growth drivers and inhibitors, including ...
Breaking Medicine Technology: