{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T15:37:51Z","timestamp":1791819471326,"version":"4.3.4"},"reference-count":0,"publisher":"Oxford University Press (OUP)","issue":"6","content-domain":{"domain":["eje.bioscientifica.com"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2021,6,1]]},"abstract":"<jats:sec>\n<jats:title>Background<\/jats:title>\n<jats:p>The response of advanced adrenocortical carcinoma (ACC) to current chemotherapies is unsatisfactory and a limited rate of response to immunotherapy was observed in clinical trials. High tumour mutational burden (TMB) and the presence of a specific DNA signature are characteristic features of tumours with mutations in the gene <jats:italic>MUTYH<\/jats:italic> encoding the mutY DNA glycosylase. Both have been shown to potentially predict the response to immunotherapy. High TMB in an ACC cell line model has not been reported yet.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Design and methods<\/jats:title>\n<jats:p>The JIL-2266 cell line was established from a primary ACC tumour, comprehensively characterised and oxidative damage, caused by a dysfunctional mutY DNA glycosylase, confirmed.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Results<\/jats:title>\n<jats:p>Here, we characterise the novel patient-derived ACC cell line JIL-2266, which is deficient in mutY-dependent DNA repair. JIL-2266 cells have a consistent STR marker profile that confirmed congruousness with primary ACC tumour. Cells proliferate with a doubling time of 41 \u00b1 13 h. Immunohistochemistry revealed positivity for steroidogenic factor-1. Mass spectrometry did not demonstrate significant steroid hormone synthesis. JIL-2266 have hemizygous mutations in the tumour suppressor gene <jats:italic>TP53<\/jats:italic> (c.859G&gt;T:p.E287X) and <jats:italic>MUTYH<\/jats:italic> (c.316C&gt;T:p.R106W). Exome sequencing showed 683 single nucleotide variants and 4 insertions\/deletions. We found increased oxidative DNA damage in the cell line and the corresponding primary tumour caused by impaired mutY DNA glycosylase function and accumulation of 8-oxoguanine.<\/jats:p>\n<\/jats:sec>\n<jats:sec>\n<jats:title>Conclusion<\/jats:title>\n<jats:p>This model will be valuable as a pre-clinical ACC cell model with high TMB and a tool to study oxidative DNA damage in the adrenal gland.<\/jats:p>\n<\/jats:sec>","DOI":"10.1530\/eje-20-1423","type":"journal-article","created":{"date-parts":[[2021,4,8]],"date-time":"2021-04-08T17:10:14Z","timestamp":1617901814000},"page":"823-835","update-policy":"https:\/\/doi.org\/10.1530\/crossmarkpolicy-7","source":"Crossref","is-referenced-by-count":31,"title":["A novel patient-derived cell line of adrenocortical carcinoma shows a pathogenic role of germline MUTYH mutation and high tumour mutational burden"],"prefix":"10.1093","volume":"184","author":[{"given":"Laura-Sophie","family":"Landwehr","sequence":"first","affiliation":[{"name":"1Division of Endocrinology and Diabetology Department of Internal Medicine I, University Hospital, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jochen","family":"Schreiner","sequence":"additional","affiliation":[{"name":"1Division of Endocrinology and Diabetology Department of Internal Medicine I, University Hospital, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silke","family":"Appenzeller","sequence":"additional","affiliation":[{"name":"2Comprehensive Cancer Center Mainfranken, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefan","family":"Kircher","sequence":"additional","affiliation":[{"name":"3Institute of Pathology, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sabine","family":"Herterich","sequence":"additional","affiliation":[{"name":"4Clinical Chemistry and Laboratory Medicine, University Hospital, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Silviu","family":"Sbiera","sequence":"additional","affiliation":[{"name":"1Division of Endocrinology and Diabetology Department of Internal Medicine I, University Hospital, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martin","family":"Fassnacht","sequence":"additional","affiliation":[{"name":"1Division of Endocrinology and Diabetology Department of Internal Medicine I, University Hospital, University of W\u00fcrzburg, W\u00fcrzburg, Germany"},{"name":"2Comprehensive Cancer Center Mainfranken, University of W\u00fcrzburg, W\u00fcrzburg, Germany"},{"name":"4Clinical Chemistry and Laboratory Medicine, University Hospital, University of W\u00fcrzburg, W\u00fcrzburg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"Kroiss","sequence":"additional","affiliation":[{"name":"1Division of Endocrinology and Diabetology Department of Internal Medicine I, University Hospital, University of W\u00fcrzburg, W\u00fcrzburg, Germany"},{"name":"2Comprehensive Cancer Center Mainfranken, University of W\u00fcrzburg, W\u00fcrzburg, Germany"},{"name":"5Department of Medicine IV, University Hospital Munich, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isabel","family":"Weigand","sequence":"additional","affiliation":[{"name":"1Division of Endocrinology and Diabetology Department of Internal Medicine I, University Hospital, University of W\u00fcrzburg, W\u00fcrzburg, Germany"},{"name":"5Department of Medicine IV, University Hospital Munich, Ludwig-Maximilians-Universit\u00e4t M\u00fcnchen, Munich, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","container-title":["European Journal of 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