Loss of DAXX/ATRX expression and alternative lengthening of telomeres in insulinomas and neuroendocrine tumours of the small intestine

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dc.contributor.advisor Sipos, Bence (Prof. Dr.)
dc.contributor.author Neumayer, Bettina
dc.date.accessioned 2015-09-29T05:16:28Z
dc.date.available 2015-09-29T05:16:28Z
dc.date.issued 2015-09
dc.identifier.other 445875933 de_DE
dc.identifier.uri http://hdl.handle.net/10900/65117
dc.identifier.uri http://nbn-resolving.de/urn:nbn:de:bsz:21-dspace-651177 de_DE
dc.identifier.uri http://dx.doi.org/10.15496/publikation-6537
dc.description.abstract Neuroendocrine tumours (NETs) are rare neoplasms with an incidence of 2- 4% per 100,000 population. Most NETs are found in the pancreas (34.2%) and the small intestine (25.8%). At time of diagnosis, 50% of all patients with NETs already have metastasis and systemic therapy is indicated. There are drugs available like somatostatin- analogues, inhibitors of the mTOR pathway and inhibitors of angiogenesis and interferon alpha. For Somatostatin- analogues a stabilisation of tumour growth is reported. The other drugs showed a prolonged survival time for months compared to placebo. However, a better understanding of the biological mechanisms of this tumour type is necessary in order to find drugs for targeted therapy. Recent studies reported that mutations in the MEN1 gene, in the DAXX/ATRX gene and in genes related to the mTOR pathway are found in pancreatic neuroendocrine tumours (PANETs). Our aim is to examine the significance of DAXX/ATRX expression and alternative lengthening of telomeres (ALT) in insulinomas, which has been investigated in PANETs, but only for a small number of insulinomas. We also address this question in NETs of the small intestine (siNETs), which has not been examined at all. We found a loss of DAXX expression in one insulinoma and a loss of ATRX expression in four insulinomas. These results correlate with ALT phenotype (p< 0.001). We revealed that a loss of DAXX/ATRX is strongly correlated with malignant behaviour (p< 0.001), a bigger tumour size(p= 0.005) and a shortened overall survival (p=0.012). In other words, finding DAXX/ATRX expression loss in insulinomas is a sign of malignancy and a poor prognosis. In siNETs, loss of DAXX/ATRX expression and ALT phenotype play a minor role in the tumourgenesis. The ALT pathway plays an important role in insulinomas and PANETs in general, therefore further studies are required to find new agents for a targeted therapy. en
dc.language.iso en de_DE
dc.publisher Universität Tübingen de_DE
dc.rights ubt-podno de_DE
dc.rights.uri http://tobias-lib.uni-tuebingen.de/doku/lic_ohne_pod.php?la=de de_DE
dc.rights.uri http://tobias-lib.uni-tuebingen.de/doku/lic_ohne_pod.php?la=en en
dc.subject.classification Insulinom de_DE
dc.subject.ddc 610 de_DE
dc.subject.other neuroendocrine tumours of the small intestine en
dc.subject.other telomeres en
dc.subject.other Telomer de_DE
dc.subject.other alternative lengthening of telomeres en
dc.subject.other neuroendokrine Tumoren des Dünndarms de_DE
dc.subject.other ATRX de_DE
dc.subject.other DAXX de_DE
dc.subject.other Alternative Verlängerung der Telomere de_DE
dc.title Loss of DAXX/ATRX expression and alternative lengthening of telomeres in insulinomas and neuroendocrine tumours of the small intestine en
dc.type Dissertation de_DE
dcterms.dateAccepted 2015-09-09
utue.publikation.fachbereich Medizinische Fakultät de_DE
utue.publikation.fakultaet 4 Medizinische Fakultät de_DE
utue.publikation.fakultaet 4 Medizinische Fakultät de_DE

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