{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T05:54:46Z","timestamp":1789538086736,"version":"build-2803163510"},"reference-count":63,"publisher":"Bioscientifica","issue":"8","license":[{"start":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T00:00:00Z","timestamp":1784505600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["journals.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2026,8,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Patients with pancreatic neuroendocrine tumours (PNETs) often have similar baseline clinical characteristics, including grade and molecular imaging phenotype, yet have highly variable responses to peptide receptor radionuclide therapy (PRRT). To identify genomic alterations and mutational patterns associated with PRRT treatment response and acquired somatic changes following PRRT exposure, whole genome or exome sequencing was applied to 40 PNET samples from 32 patients, including eight paired pre- or post-PRRT samples. The genomic profile of tumours reflected the known mutational landscape of PNET with MEN1 (34%), ATRX\/DAXX (47%) alterations and a recurrent pattern of aneuploidy (38%) detected. A recurrent PSIP1::TBL1X fusion of unknown function was also identified in four tumours. The disease control rate following PRRT using RECIST1.1 and molecular imaging criteria was 88% (28\/32). No mutational features were found to be statistically associated with progression-free survival. There was no significant increase in tumour mutational burden in the post-PRRT tumours, nor recurrent emergent mutational changes in cancer driver genes to explain progression to higher-grade disease, when observed. However, a small indel signature (ID8) previously associated with DNA damage repair by non-homologous end joining (NHEJ) was higher in PRRT-exposed compared with PRRT-naive samples (23.8 vs 4.8%, respectively; P &amp;lt; 0.001). Thus, comprehensive DNA analysis of pancreatic NETs did not identify biomarkers predictive of PRRT response nor evidence for high-level PRRT-induced genomic instability or hypermutation, yet mutation signature analysis supports NHEJ as being important for DNA repair and survival of neuroendocrine cells following exposure to beta-particle radiation.<\/jats:p>","DOI":"10.1530\/erc-26-0207","type":"journal-article","created":{"date-parts":[[2026,7,20]],"date-time":"2026-07-20T09:48:28Z","timestamp":1784540908000},"update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-8","source":"Crossref","is-referenced-by-count":1,"title":["Whole genome and exome sequencing of pancreatic neuroendocrine tumours to investigate PRRT response"],"prefix":"10.1530","volume":"33","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7631-9147","authenticated-orcid":true,"given":"Emma","family":"Boehm","sequence":"first","affiliation":[{"name":"Department of Clinical Pathology, The University of Melbourne 1 , , ,","place":["Parkville, Victoria, Australia"]},{"name":"Collaborative Centre for Genomic Cancer Medicine, The University of Melbourne 2 , , ,","place":["Parkville, Victoria, Australia"]},{"name":"Department of Cancer Imaging, Peter MacCallum Cancer Centre 3 , , ,","place":["Melbourne, Victoria, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aidan","family":"Flynn","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology, The University of Melbourne 1 , , ,","place":["Parkville, Victoria, Australia"]},{"name":"Collaborative Centre for Genomic Cancer Medicine, The University of Melbourne 2 , , ,","place":["Parkville, Victoria, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alex","family":"Caneborg","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology, The University of Melbourne 1 , , ,","place":["Parkville, Victoria, 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Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise","family":"Jackett","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology, Peter MacCallum Cancer Centre 6 , , ,","place":["Melbourne, Victoria, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Owen W J","family":"Prall","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology, Peter MacCallum Cancer Centre 6 , , ,","place":["Melbourne, Victoria, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Mitchell","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology, Peter MacCallum Cancer Centre 6 , , ,","place":["Melbourne, Victoria, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace","family":"Kong","sequence":"additional","affiliation":[{"name":"Department of Cancer Imaging, Peter MacCallum Cancer Centre 3 , , ,","place":["Melbourne, Victoria, Australia"]},{"name":"Sir Peter MacCallum Department of Oncology, University of Melbourne 5 , , ,","place":["Melbourne, Victoria, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Michael","sequence":"additional","affiliation":[{"name":"Sir Peter MacCallum Department of Oncology, University of Melbourne 5 , , ,","place":["Melbourne, Victoria, Australia"]},{"name":"Department of Medical Oncology, Peter MacCallum Cancer Centre 7 , , ,","place":["Melbourne, Victoria, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"Akhurst","sequence":"additional","affiliation":[{"name":"Department of Cancer Imaging, Peter MacCallum Cancer Centre 3 , , ,","place":["Melbourne, Victoria, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Benjamin N J","family":"Thomson","sequence":"additional","affiliation":[{"name":"Department of Surgical Oncology, Peter MacCallum Cancer Centre 8 , , ,","place":["Parkville, Victoria, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"William K","family":"Murray","sequence":"additional","affiliation":[{"name":"Department of Anatomical Pathology, Peter MacCallum Cancer Centre 6 , , ,","place":["Melbourne, Victoria, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kwang","family":"Chin","sequence":"additional","affiliation":[{"name":"Department of Cancer Imaging, Peter MacCallum Cancer Centre 3 , , ,","place":["Melbourne, Victoria, Australia"]},{"name":"Sir Peter MacCallum Department of Oncology, University of Melbourne 5 , , ,","place":["Melbourne, Victoria, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben","family":"Lawrence","sequence":"additional","affiliation":[{"name":"Department of Oncology, Faculty of Medicine and Health Sciences, University of Auckland 9 , ,","place":["Auckland, New Zealand"]},{"name":"Maurice Wilkins Centre for Biodiscovery Hosted by The University of Auckland 10 , ,","place":["Auckland, New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cristin G","family":"Print","sequence":"additional","affiliation":[{"name":"Maurice Wilkins Centre for Biodiscovery Hosted by The University of Auckland 10 , ,","place":["Auckland, New Zealand"]},{"name":"Department of Molecular Medicine and Pathology, Faculty of Medical and Health Sciences, University of Auckland 11 , ,","place":["Auckland, New Zealand"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joseph H A","family":"Vissers","sequence":"additional","affiliation":[{"name":"Department of Clinical Pathology, The University of Melbourne 1 , , ,","place":["Parkville, Victoria, Australia"]},{"name":"Collaborative Centre for Genomic Cancer Medicine, The University of Melbourne 2 , , ,","place":["Parkville, Victoria, Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sean 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