{"entity": "journal", "iuid": "5ed4b9e6e24348e0a5f92eba308d6702", "timestamp": "2026-07-20T12:31:27.140Z", "links": {"self": {"href": "https://publications.scilifelab.se/journal/Endocr.%20Relat.%20Cancer.json"}, "display": {"href": "https://publications.scilifelab.se/journal/Endocr.%20Relat.%20Cancer"}}, "title": "Endocr. Relat. Cancer", "issn": "1479-6821", "issn-l": "1351-0088", "publications_count": 5, "publications": [{"entity": "publication", "iuid": "cd69deb28cb34a7ba0f06bcbdcde1b23", "links": {"self": {"href": "https://publications.scilifelab.se/publication/cd69deb28cb34a7ba0f06bcbdcde1b23.json"}, "display": {"href": "https://publications.scilifelab.se/publication/cd69deb28cb34a7ba0f06bcbdcde1b23"}}, "title": "Role of GDH and PARP inhibitors as novel treatments for SDHB-deficient PPGLs.", "authors": [{"family": "Tabebi", "given": "Mouna", "initials": "M", "orcid": "0000-0002-2873-161X", "researcher": {"href": "https://publications.scilifelab.se/researcher/285705c043f34b55826e7f33ab36a875.json"}}, {"family": "Abdallah", "given": "Sallam", "initials": "S"}, {"family": "El-Serafi", "given": "Ahmed", "initials": "A"}, {"family": "S\u00f6derkvist", "given": "Peter", "initials": "P", "orcid": "0000-0001-9867-8706", "researcher": {"href": "https://publications.scilifelab.se/researcher/c1fc163b9a08421180f7f235af3897f4.json"}}, {"family": "Gimm", "given": "Oliver", "initials": "O", "orcid": "0000-0002-0054-664X", "researcher": {"href": "https://publications.scilifelab.se/researcher/9879641fb40042ae90ff034f4912a16d.json"}}], "type": "journal article", "published": "2025-10-01", "journal": {"title": "Endocr. Relat. Cancer", "issn": "1479-6821", "issn-l": "1351-0088", "volume": "32", "issue": "10", "pages": null}, "abstract": "SDHB, one of the four genes encoding the subunits of the Krebs cycle enzyme succinate dehydrogenase (SDH), acts as a tumor suppressor in several human cancers, including pheochromocytomas/paragangliomas. Mutations in SDHB lead to a reduction or complete loss of enzymatic activity, linking SDHB to paraganglioma malignancy. Given the difficulty in curing metastatic paragangliomas and the limited value of surgery, new treatments are needed. Glutamine dehydrogenase 1 (GDH1), a key regulator of glutathione metabolism, and poly (ADP-ribose) polymerase (PARP), essential for repairing single- or double-stranded DNA breaks, are crucial in cancer initiation and progression. We treated the human pheochromocytoma cell line (hPheo1) with knocked-down SDHB using radiation, the GDH inhibitor 'R162', and the PARP inhibitor 'olaparib'. Combining R162 with radiation enhances anticancer effectiveness, reduces cell proliferation, and causes G2/M phase arrest in the wild-type and KD-SDHB hPheo1 cell line. KD-SDHB hPheo1 cells treated with olaparib alone were more resistant than wild-type cells but were more sensitive in combination with radiation, activated repair mechanisms, and halted cell cycle progression at the G2/M phase. These results suggest that enhancing radiation-induced DNA damage could be a potential treatment strategy for metastatic pheochromocytomas/paragangliomas. Inhibiting GDH1 and PARP activities, with radiation, may represent promising strategies for the treatment of SDHB-deficient pheochromocytoma/paraganglioma; however, their effects do not appear to be specific to SDHB-deficient cells and require further validation.", "doi": "10.1530/ERC-25-0173", "pmid": "40990469", "labels": {"Clinical Genomics": "Collaborative", "Clinical Genomics Link\u00f6ping": "Collaborative"}, "xrefs": [{"db": "pii", "key": "ERC-25-0173"}], "notes": [], "created": "2025-10-09T06:57:26.582Z", "modified": "2025-11-04T09:44:51.833Z"}, {"entity": "publication", "iuid": "8949ae798885446eb4b442de770a73dd", "links": {"self": {"href": "https://publications.scilifelab.se/publication/8949ae798885446eb4b442de770a73dd.json"}, "display": {"href": "https://publications.scilifelab.se/publication/8949ae798885446eb4b442de770a73dd"}}, "title": "Nuclear and mitochondrial DNA alterations in pheochromocytomas and paragangliomas, and their potential treatment.", "authors": [{"family": "Tabebi", "given": "Mouna", "initials": "M", "orcid": "0000-0002-2873-161X", "researcher": {"href": "https://publications.scilifelab.se/researcher/285705c043f34b55826e7f33ab36a875.json"}}, {"family": "S\u00f6derkvist", "given": "Peter", "initials": "P"}, {"family": "Gimm", "given": "Oliver", "initials": "O"}], "type": "journal article", "published": "2023-01-01", "journal": {"title": "Endocr. Relat. Cancer", "issn": "1479-6821", "volume": "30", "issue": "1", "issn-l": "1351-0088"}, "abstract": "Mitochondrial DNA (mtDNA) alterations have been reported in different types of cancers and are suggested to play important roles in cancer development and metastasis. However, there is little information about its involvement in pheochromocytomas and paragangliomas (PCCs/PGLs) formation. PCCs and PGLs are rare endocrine tumors of the chromaffin cells in the adrenal medulla and extra-adrenal paraganglia that can synthesize and secrete catecholamines. Over the last 3 decades, the genetic background of about 60% of PCCs/PGLs involving nuclear DNA alterations has been determined. Recently, a study showed that mitochondrial alterations can be found in around 17% of the remaining PCCs/PGLs. In this review, we summarize recent knowledge regarding both nuclear and mitochondrial alterations and their involvement in PCCs/PGLs. We also provide brief insights into the genetics and the molecular pathways associated with PCCs/PGLs and potential therapeutical targets.", "doi": "10.1530/ERC-22-0217", "pmid": "36219865", "labels": {"Clinical Genomics Link\u00f6ping": "Collaborative", "Clinical Genomics": "Collaborative"}, "xrefs": [{"db": "pii", "key": "ERC-22-0217"}], "notes": [], "created": "2023-12-03T06:08:55.703Z", "modified": "2023-12-03T06:08:55.727Z"}, {"entity": "publication", "iuid": "318bfeaef13a4c66999ad19c817f92ae", "links": {"self": {"href": "https://publications.scilifelab.se/publication/318bfeaef13a4c66999ad19c817f92ae.json"}, "display": {"href": "https://publications.scilifelab.se/publication/318bfeaef13a4c66999ad19c817f92ae"}}, "title": "The neuroendocrine phenotype, genomic profile and therapeutic sensitivity of GEPNET cell lines.", "authors": [{"family": "Hofving", "given": "Tobias", "initials": "T"}, {"family": "Arvidsson", "given": "Yvonne", "initials": "Y"}, {"family": "Almobarak", "given": "Bilal", "initials": "B"}, {"family": "Inge", "given": "Linda", "initials": "L"}, {"family": "Pfragner", "given": "Roswitha", "initials": "R"}, {"family": "Persson", "given": "Marta", "initials": "M"}, {"family": "Stenman", "given": "G\u00f6ran", "initials": "G"}, {"family": "Kristiansson", "given": "Erik", "initials": "E"}, {"family": "Johanson", "given": "Viktor", "initials": "V"}, {"family": "Nilsson", "given": "Ola", "initials": "O"}], "type": "journal article", "published": "2018-03-00", "journal": {"volume": "25", "issn": "1479-6821", "issue": "3", "pages": "367-380", "title": "Endocr. Relat. Cancer", "issn-l": "1351-0088"}, "abstract": "Experimental models of neuroendocrine tumour disease are scarce, and no comprehensive characterisation of existing gastroenteropancreatic neuroendocrine tumour (GEPNET) cell lines has been reported. In this study, we aimed to define the molecular characteristics and therapeutic sensitivity of these cell lines. We therefore performed immunophenotyping, copy number profiling, whole-exome sequencing and a large-scale inhibitor screening of seven GEPNET cell lines. Four cell lines, GOT1, P-STS, BON-1 and QGP-1, displayed a neuroendocrine phenotype while three others, KRJ-I, L-STS and H-STS, did not. Instead, these three cell lines were identified as lymphoblastoid. Characterisation of remaining authentic GEPNET cell lines by copy number profiling showed that GOT1, among other chromosomal alterations, harboured losses on chromosome 18 encompassing the SMAD4 gene, while P-STS had a loss on 11q. BON-1 had a homozygous loss of CDKN2A and CDKN2B, and QGP-1 harboured amplifications of MDM2 and HMGA2 Whole-exome sequencing revealed both disease-characteristic mutations (e.g. ATRX mutation in QGP-1) and, for patient tumours, rare genetic events (e.g. TP53 mutation in P-STS, BON-1 and QGP-1). A large-scale inhibitor screening showed that cell lines from pancreatic NETs to a greater extent, when compared to small intestinal NETs, were sensitive to inhibitors of MEK. Similarly, neuroendocrine NET cells originating from the small intestine were considerably more sensitive to a group of HDAC inhibitors. Taken together, our results provide a comprehensive characterisation of GEPNET cell lines, demonstrate their relevance as neuroendocrine tumour models and explore their therapeutic sensitivity to a broad range of inhibitors.", "doi": "10.1530/ERC-17-0445", "pmid": "29444910", "labels": {"Integrated Microscopy Technologies Gothenburg": "Service"}, "xrefs": [{"db": "pii", "key": "25/3/367"}, {"db": "pmc", "key": "PMC5827037"}], "notes": [], "created": "2020-01-23T16:50:26.664Z", "modified": "2021-07-05T14:11:12.407Z"}, {"entity": "publication", "iuid": "00efcc10c8fe4acdb9bdc477e661536f", "links": {"self": {"href": "https://publications.scilifelab.se/publication/00efcc10c8fe4acdb9bdc477e661536f.json"}, "display": {"href": "https://publications.scilifelab.se/publication/00efcc10c8fe4acdb9bdc477e661536f"}}, "title": "A MUTYH germline mutation is associated with small intestinal neuroendocrine tumors.", "authors": [{"family": "Dumanski", "given": "Jan P", "initials": "JP"}, {"family": "Rasi", "given": "Chiara", "initials": "C"}, {"family": "Bj\u00f6rklund", "given": "Peyman", "initials": "P"}, {"family": "Davies", "given": "Hanna", "initials": "H"}, {"family": "Ali", "given": "Abir S", "initials": "AS"}, {"family": "Gr\u00f6nberg", "given": "Malin", "initials": "M"}, {"family": "Welin", "given": "Staffan", "initials": "S"}, {"family": "Sorbye", "given": "Halfdan", "initials": "H"}, {"family": "Gr\u00f8nb\u00e6k", "given": "Henning", "initials": "H"}, {"family": "Cunningham", "given": "Janet L", "initials": "JL"}, {"family": "Forsberg", "given": "Lars A", "initials": "LA"}, {"family": "Lind", "given": "Lars", "initials": "L"}, {"family": "Ingelsson", "given": "Erik", "initials": "E"}, {"family": "St\u00e5lberg", "given": "Peter", "initials": "P"}, {"family": "Hellman", "given": "Per", "initials": "P"}, {"family": "Tiensuu Janson", "given": "Eva", "initials": "E"}], "type": "journal article", "published": "2017-08-00", "journal": {"volume": "24", "issn": "1479-6821", "issue": "8", "pages": "427-443", "title": "Endocr. Relat. Cancer", "issn-l": "1351-0088"}, "abstract": "The genetics behind predisposition to small intestinal neuroendocrine tumors (SI-NETs) is largely unknown, but there is growing awareness of a familial form of the disease. We aimed to identify germline mutations involved in the carcinogenesis of SI-NETs. The strategy included next-generation sequencing of exome- and/or whole-genome of blood DNA, and in selected cases, tumor DNA, from 24 patients from 15 families with the history of SI-NETs. We identified seven candidate mutations in six genes that were further studied using 215 sporadic SI-NET patients. The result was compared with the frequency of the candidate mutations in three control cohorts with a total of 35,688 subjects. A heterozygous variant causing an amino acid substitution p.(Gly396Asp) in the MutY DNA glycosylase gene (MUTYH) was significantly enriched in SI-NET patients (minor allele frequencies 0.013 and 0.003 for patients and controls respectively) and resulted in odds ratio of 5.09 (95% confidence interval 1.56-14.74; P value\u2009=\u20090.0038). We also found a statistically significant difference in age at diagnosis between familial and sporadic SI-NETs. MUTYH is involved in the protection of DNA from mutations caused by oxidative stress. The inactivation of this gene leads to specific increase of G:C-\u2009>\u2009T:A transversions in DNA sequence and has been shown to cause various cancers in humans and experimental animals. Our results suggest that p.(Gly396Asp) in MUTYH, and potentially other mutations in additional members of the same DNA excision-repair pathway (such as the OGG1 gene) might be involved in driving the tumorigenesis leading to familial and sporadic SI-NETs.", "doi": "10.1530/ERC-17-0196", "pmid": "28634180", "labels": {"National Genomics Infrastructure": "Service", "NGI Stockholm (Genomics Applications)": "Service", "NGI Stockholm (Genomics Production)": "Service", "NGI Uppsala (Uppsala Genome Center)": "Service", "Bioinformatics Support for Computational Resources": "Service"}, "xrefs": [{"db": "pii", "key": "ERC-17-0196"}, {"db": "pmc", "key": "PMC5527373"}], "notes": [], "created": "2017-10-17T09:23:36.141Z", "modified": "2024-01-16T13:48:47.705Z"}, {"entity": "publication", "iuid": "6e10f1c896cf4b118659fd2d84d909c6", "links": {"self": {"href": "https://publications.scilifelab.se/publication/6e10f1c896cf4b118659fd2d84d909c6.json"}, "display": {"href": "https://publications.scilifelab.se/publication/6e10f1c896cf4b118659fd2d84d909c6"}}, "title": "Global DNA methylation patterns through an array-based approach in small intestinal neuroendocrine tumors.", "authors": [{"family": "Verdugo", "given": "Alberto Delgado", "initials": "AD"}, {"family": "Crona", "given": "Joakim", "initials": "J"}, {"family": "Starker", "given": "Lee", "initials": "L"}, {"family": "St\u00e5lberg", "given": "Peter", "initials": "P"}, {"family": "\u00c5kerstr\u00f6m", "given": "G\u00f6ran", "initials": "G"}, {"family": "Westin", "given": "Gunnar", "initials": "G"}, {"family": "Hellman", "given": "Per", "initials": "P"}, {"family": "Bj\u00f6rklund", "given": "Peyman", "initials": "P"}], "type": "letter", "published": "2014-02-00", "journal": {"volume": "21", "issn": "1479-6821", "issue": "1", "pages": "L5-L7", "title": "Endocr. Relat. Cancer", "issn-l": "1351-0088"}, "abstract": null, "doi": "10.1530/ERC-13-0481", "pmid": "24192231", "labels": {"National Genomics Infrastructure": null, "NGI Stockholm (Genomics Applications)": null, "NGI Stockholm (Genomics Production)": null}, "xrefs": [{"db": "pii", "key": "ERC-13-0481"}], "notes": [], "created": "2017-05-04T14:58:30.933Z", "modified": "2020-01-21T13:56:02.873Z"}], "created": "2017-05-09T09:12:02.389Z", "modified": "2020-11-27T13:14:04.123Z"}