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LIBRIS Formathandbok  (Information om MARC21)
00003732naa a22003853a 4500
008080901s2017 xx |||| |0|| 0|eng d
024a 10.21873/anticanres.113672 doi
024a 281793202 pmid
024a urn:nbn:se:uu:diva-3206692 urn
040 a (SwePub)uu
042 9 SwePub
072 7a ref2 swepub-contenttype
072 7a art2 swepub-publicationtype
072 7a ref2 swepub-contenttype
100a Backman, Samuel,u Uppsala universitet, Experimentell kirurgi4 aut0 (SwePub:uu)
2451 0a Detection of Somatic Mutations in Gastroenteropancreatic Neuroendocrine Tumors Using Targeted Deep Sequencing
500 a Published
500 a 6
5208 enga <p>Mutations affecting the mechanistic target of rapamycin (MTOR) signalling pathway are frequent in human cancer and have been identified in up to 15% of pancreatic neuroendocrine tumours (NETs). Grade A evidence supports the efficacy of MTOR inhibition with everolimus in pancreatic NETs. Although a significant proportion of patients experience disease stabilization, only a minority will show objective tumour responses. It has been proposed that genomic mutations resulting in activation of MTOR signalling could be used to predict sensitivity to everolimus.</p><p><strong>PATIENTS AND METHODS:</strong> Patients with NETs that underwent treatment with everolimus at our Institution were identified and those with available tumour tissue were selected for further analysis. Targeted next-generation sequencing (NGS) was used to re-sequence 22 genes that were selected on the basis of documented involvement in the MTOR signalling pathway or in the tumourigenesis of gastroenterpancreatic NETs. Radiological responses were documented using Response Evaluation Criteria in Solid Tumours.</p><p><strong>RESULTS:</strong> Six patients were identified, one had a partial response and four had stable disease. Sequencing of tumour tissue resulted in a median sequence depth of 667.1 (range=404-1301) with 1-fold coverage of 95.9-96.5% and 10-fold coverage of 87.6-92.2%. A total of 494 genetic variants were discovered, four of which were identified as pathogenic. All pathogenic variants were validated using Sanger sequencing and were found exclusively in menin 1 (MEN1) and death domain associated protein (DAXX) genes. No mutations in the MTOR pathway-related genes were observed.</p><p><strong>CONCLUSION:</strong> Targeted NGS is a feasible method with high diagnostic yield for genetic characterization of pancreatic NETs. A potential association between mutations in NETs and response to everolimus should be investigated by future studies.</p>
650 7a MEDICIN OCH HÄLSOVETENSKAPx Klinisk medicinx Cancer och onkologi2 hsv//swe0 (SwePub)30203
650 7a MEDICAL AND HEALTH SCIENCESx Clinical Medicinex Cancer and Oncology2 hsv//eng0 (SwePub)30203
653 a MTOR
653 a PNET
653 a biomarker
653 a next-generation sequencing
700a Norlén, Olov,u Uppsala universitet, Endokrinkirurgi4 aut0 (SwePub:uu)
700a Eriksson, Barbro,u Uppsala universitet, Endokrin tumörbiologi4 aut0 (SwePub:uu)
700a Skogseid, Britt,u Uppsala universitet, Endokrin tumörbiologi4 aut0 (SwePub:uu)
700a Stålberg, Peter,u Uppsala universitet, Endokrinkirurgi4 aut0 (SwePub:uu)
700a Crona, Joakim,u Uppsala universitet, Endokrin tumörbiologi4 aut0 (SwePub:uu)
773t Anticancer Researchx 0250-7005x 1791-7530g 37:2, s. 705-712q 37:2<705-712
8564 8u http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-320669y Till lärosätets (uu) databasx lärosäteslänk
8564 8u http://dx.doi.org/10.21873/anticanres.11367

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