{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,14]],"date-time":"2026-06-14T20:07:35Z","timestamp":1781467655462,"version":"3.54.1"},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T00:00:00Z","timestamp":1728000000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T00:00:00Z","timestamp":1728000000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100018935","name":"Universit\u00e4tsklinikum Erlangen","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100018935","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Discov Onc"],"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:p>Benign tumors, but rarely cancer, are common in patients with tuberous sclerosis complex (TSC). Blood samples from patients undergoing treatment for TSC at our institution were analyzed for their individual sensitivity to ionizing radiation. Blood samples were collected from 13 adult patients with TSC. The samples were irradiated ex vivo and analyzed by 3-color fluorescence in situ hybridization. In each patient, aberrations were analyzed in 200 metaphases of chromosomes 1, 2, and 4 and scored as breaks. Radiosensitivity was determined by mean breaks per metaphase (B\/M) and compared to both healthy donors and oncologic patients. The radiosensitivity (B\/M) of the TSC patient cohort (n\u2009=\u200913; female: 46.2%, B\/M: 0.48\u2009\u00b1\u20090.11) was clearly increased compared to healthy individuals of similar age (n\u2009=\u200990; female: 54.4%; B\/M: 0.40\u2009\u00b1\u20090.09; p\u2009=\u20090.001). There was no difference compared to age-matched oncological patients (n\u2009=\u200978; female: 67.9%; B\/M 0.49\u2009\u00b1\u20090.14; p\u2009=\u20090.246). Similarly, the proportion of radiosensitive (B\/M\u2009&gt;\u20090.5) and distinctly radiosensitive individuals (B\/M\u2009&gt;\u20090.6) was increased in the TSC and oncological patient cohorts (TSC: 30.8% and 7.7%, oncological patients: 46.2% and 14.1%) compared to the healthy individuals (11.1% and 2.2%). Although patients with TSC develop mostly benign and rarely malignant tumors, they are similarly sensitive to radiation as patients with malignant tumors.<\/jats:p>","DOI":"10.1007\/s12672-024-01395-1","type":"journal-article","created":{"date-parts":[[2024,10,4]],"date-time":"2024-10-04T13:01:43Z","timestamp":1728046903000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Radiosensitivity in individuals with tuberous sclerosis complex"],"prefix":"10.1007","volume":"15","author":[{"given":"Lukas","family":"Kuhlmann","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jenny","family":"Stritzelberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rainer","family":"Fietkau","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Luitpold V.","family":"Distel","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajo M.","family":"Hamer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,10,4]]},"reference":[{"key":"1395_CR1","doi-asserted-by":"publisher","first-page":"16035","DOI":"10.1038\/nrdp.2016.35","volume":"2","author":"EP Henske","year":"2016","unstructured":"Henske EP, Jozwiak S, Kingswood JC, Sampson JR, Thiele EA. Tuberous sclerosis complex. Nat Rev Dis Primers. 2016;2:16035. https:\/\/doi.org\/10.1038\/nrdp.2016.35.","journal-title":"Nat Rev Dis Primers"},{"issue":"1","key":"1395_CR2","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1007\/s12519-023-00762-2","volume":"20","author":"P Curatolo","year":"2024","unstructured":"Curatolo P, Scheper M, Emberti Gialloreti L, Specchio N, Aronica E. Is tuberous sclerosis complex-associated autism a preventable and treatable disorder? World J Pediatr. 2024;20(1):40\u201353. https:\/\/doi.org\/10.1007\/s12519-023-00762-2.","journal-title":"World J Pediatr"},{"issue":"9639","key":"1395_CR3","doi-asserted-by":"publisher","first-page":"657","DOI":"10.1016\/S0140-6736(08)61279-9","volume":"372","author":"P Curatolo","year":"2008","unstructured":"Curatolo P, Bombardieri R, Jozwiak S. Tuberous sclerosis. Lancet. 2008;372(9639):657\u201368. https:\/\/doi.org\/10.1016\/S0140-6736(08)61279-9.","journal-title":"Lancet"},{"issue":"SI-2","key":"1395_CR4","doi-asserted-by":"publisher","first-page":"1665","DOI":"10.3906\/sag-2002-133","volume":"50","author":"SP Uysal","year":"2020","unstructured":"Uysal SP, Sahin M. Tuberous sclerosis: a review of the past, present, and future. Turk J Med Sci. 2020;50(SI-2):1665\u201376. https:\/\/doi.org\/10.3906\/sag-2002-133.","journal-title":"Turk J Med Sci"},{"key":"1395_CR5","doi-asserted-by":"publisher","DOI":"10.3389\/fneur.2021.697467","volume":"12","author":"R Nabbout","year":"2021","unstructured":"Nabbout R, Belousova E, Benedik MP, Carter T, Cottin V, Curatolo P, et al. Historical patterns of diagnosis, treatments, and outcome of epilepsy associated with tuberous sclerosis complex: results from TOSCA registry. Front Neurol. 2021;12: 697467. https:\/\/doi.org\/10.3389\/fneur.2021.697467.","journal-title":"Front Neurol"},{"key":"1395_CR6","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1016\/j.pediatrneurol.2021.09.017","volume":"126","author":"M Nabavi Nouri","year":"2022","unstructured":"Nabavi Nouri M, Zak M, Jain P, Whitney R. Epilepsy management in tuberous sclerosis complex: existing and evolving therapies and future considerations. Pediatr Neurol. 2022;126:11\u20139. https:\/\/doi.org\/10.1016\/j.pediatrneurol.2021.09.017.","journal-title":"Pediatr Neurol"},{"key":"1395_CR7","doi-asserted-by":"publisher","first-page":"39","DOI":"10.3389\/fnana.2020.00039","volume":"14","author":"DM Feliciano","year":"2020","unstructured":"Feliciano DM. The neurodevelopmental pathogenesis of tuberous sclerosis complex (TSC). Front Neuroanat. 2020;14:39. https:\/\/doi.org\/10.3389\/fnana.2020.00039.","journal-title":"Front Neuroanat"},{"issue":"2","key":"1395_CR8","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.cell.2012.03.017","volume":"149","author":"M Laplante","year":"2012","unstructured":"Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell. 2012;149(2):274\u201393. https:\/\/doi.org\/10.1016\/j.cell.2012.03.017.","journal-title":"Cell"},{"key":"1395_CR9","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1016\/j.pediatrneurol.2016.07.003","volume":"63","author":"ES Roach","year":"2016","unstructured":"Roach ES. Applying the lessons of tuberous sclerosis: the 2015 Hower award lecture. Pediatr Neurol. 2016;63:6\u201322. https:\/\/doi.org\/10.1016\/j.pediatrneurol.2016.07.003.","journal-title":"Pediatr Neurol"},{"issue":"4","key":"1395_CR10","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.pediatrneurol.2013.08.001","volume":"49","author":"H Northrup","year":"2013","unstructured":"Northrup H, Krueger DA. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 Iinternational Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013;49(4):243\u201354. https:\/\/doi.org\/10.1016\/j.pediatrneurol.2013.08.001.","journal-title":"Pediatr Neurol"},{"key":"1395_CR11","doi-asserted-by":"publisher","first-page":"50","DOI":"10.1016\/j.pediatrneurol.2021.07.011","volume":"123","author":"H Northrup","year":"2021","unstructured":"Northrup H, Aronow ME, Bebin EM, Bissler J, Darling TN, de Vries PJ, et al. Updated international tuberous sclerosis complex diagnostic criteria and surveillance and management recommendations. Pediatr Neurol. 2021;123:50\u201366. https:\/\/doi.org\/10.1016\/j.pediatrneurol.2021.07.011.","journal-title":"Pediatr Neurol"},{"issue":"1","key":"1395_CR12","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1590\/1678-4685-GMB-2015-0321","volume":"40","author":"C Rosset","year":"2017","unstructured":"Rosset C, Netto CBO, Ashton-Prolla P. TSC1 and TSC2 gene mutations and their implications for treatment in Tuberous Sclerosis Complex: a review. Genet Mol Biol. 2017;40(1):69\u201379. https:\/\/doi.org\/10.1590\/1678-4685-GMB-2015-0321.","journal-title":"Genet Mol Biol"},{"issue":"3","key":"1395_CR13","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1093\/hmg\/ddq491","volume":"20","author":"LH Zeng","year":"2011","unstructured":"Zeng LH, Rensing NR, Zhang B, Gutmann DH, Gambello MJ, Wong M. Tsc2 gene inactivation causes a more severe epilepsy phenotype than Tsc1 inactivation in a mouse model of tuberous sclerosis complex. Hum Mol Genet. 2011;20(3):445\u201354. https:\/\/doi.org\/10.1093\/hmg\/ddq491.","journal-title":"Hum Mol Genet"},{"issue":"2","key":"1395_CR14","doi-asserted-by":"publisher","first-page":"40","DOI":"10.5306\/wjco.v14.i2.40","volume":"14","author":"EN Imyanitov","year":"2023","unstructured":"Imyanitov EN, Kuligina ES, Sokolenko AP, Suspitsin EN, Yanus GA, Iyevleva AG, et al. Hereditary cancer syndromes. World J Clin Oncol. 2023;14(2):40\u201368. https:\/\/doi.org\/10.5306\/wjco.v14.i2.40.","journal-title":"World J Clin Oncol"},{"issue":"1","key":"1395_CR15","doi-asserted-by":"publisher","first-page":"102","DOI":"10.1007\/s00066-022-01981-8","volume":"199","author":"S Ben Dhia","year":"2023","unstructured":"Ben Dhia S, Berthou H, Warcoin M, Rodrigues M, Noret A, Beddok A, et al. Combined-modality treatment for locally advanced cervical cancer in a woman with Bloom-like syndrome: a case report and review of the literature. Strahlenther Onkol. 2023;199(1):102\u20135. https:\/\/doi.org\/10.1007\/s00066-022-01981-8.","journal-title":"Strahlenther Onkol"},{"key":"1395_CR16","doi-asserted-by":"publisher","DOI":"10.3390\/ijms22137158","author":"L El-Nachef","year":"2021","unstructured":"El-Nachef L, Al-Choboq J, Restier-Verlet J, Granzotto A, Berthel E, Sonzogni L, et al. Human radiosensitivity and radiosusceptibility: what are the differences? Int J Mol Sci. 2021. https:\/\/doi.org\/10.3390\/ijms22137158.","journal-title":"Int J Mol Sci"},{"issue":"1 suppl. 1","key":"1395_CR17","doi-asserted-by":"publisher","DOI":"10.1590\/1678-4685-GMB-2019-0085","volume":"43","author":"AT Vessoni","year":"2020","unstructured":"Vessoni AT, Guerra CCC, Kajitani GS, Nascimento LLS, Garcia CCM. Cockayne Syndrome: the many challenges and approaches to understand a multifaceted disease. Genet Mol Biol. 2020;43(1 suppl. 1): e20190085. https:\/\/doi.org\/10.1590\/1678-4685-GMB-2019-0085.","journal-title":"Genet Mol Biol"},{"issue":"23","key":"1395_CR18","doi-asserted-by":"publisher","first-page":"3673","DOI":"10.1002\/cncr.30248","volume":"122","author":"PL Mai","year":"2016","unstructured":"Mai PL, Best AF, Peters JA, DeCastro RM, Khincha PP, Loud JT, et al. Risks of first and subsequent cancers among TP53 mutation carriers in the National Cancer Institute Li-Fraumeni syndrome cohort. Cancer. 2016;122(23):3673\u201381. https:\/\/doi.org\/10.1002\/cncr.30248.","journal-title":"Cancer"},{"issue":"1","key":"1395_CR19","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1097\/CCO.0000000000000423","volume":"30","author":"A Amadou","year":"2018","unstructured":"Amadou A, Achatz MIW, Hainaut P. Revisiting tumor patterns and penetrance in germline TP53 mutation carriers: temporal phases of Li-Fraumeni syndrome. Curr Opin Oncol. 2018;30(1):23\u20139. https:\/\/doi.org\/10.1097\/CCO.0000000000000423.","journal-title":"Curr Opin Oncol"},{"issue":"3","key":"1395_CR20","doi-asserted-by":"publisher","first-page":"312","DOI":"10.1667\/0033-7587(2002)157[0312:ROATAN]2.0.CO;2","volume":"157","author":"S Neubauer","year":"2002","unstructured":"Neubauer S, Arutyunyan R, Stumm M, Dork T, Bendix R, Bremer M, et al. Radiosensitivity of ataxia telangiectasia and Nijmegen breakage syndrome homozygotes and heterozygotes as determined by three-color FISH chromosome painting. Radiat Res. 2002;157(3):312\u201321.","journal-title":"Radiat Res"},{"issue":"1\u20134","key":"1395_CR21","doi-asserted-by":"publisher","first-page":"365","DOI":"10.1159\/000077517","volume":"104","author":"D Scott","year":"2004","unstructured":"Scott D. Chromosomal radiosensitivity and low penetrance predisposition to cancer. Cytogenet Genome Res. 2004;104(1\u20134):365\u201370.","journal-title":"Cytogenet Genome Res"},{"issue":"5","key":"1395_CR22","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1007\/s000660050005","volume":"176","author":"D Scott","year":"2000","unstructured":"Scott D. Chromosomal radiosensitivity, cancer predisposition and response to radiotherapy. Strahlenther Onkol. 2000;176(5):229\u201334.","journal-title":"Strahlenther Onkol"},{"issue":"1","key":"1395_CR23","doi-asserted-by":"publisher","first-page":"98","DOI":"10.1186\/s13014-023-02291-8","volume":"18","author":"D Rzepka","year":"2023","unstructured":"Rzepka D, Schenker H, Geinitz H, Silberberger E, Kaudewitz D, Schuster B, et al. Chromosomal radiosensitivity in oncological and non-oncological patients with rheumatoid arthritis and connective tissue diseases. Radiat Oncol. 2023;18(1):98. https:\/\/doi.org\/10.1186\/s13014-023-02291-8.","journal-title":"Radiat Oncol"},{"issue":"8","key":"1395_CR24","doi-asserted-by":"publisher","first-page":"6618","DOI":"10.3390\/cimb45080418","volume":"45","author":"T Zuhair Kassem","year":"2023","unstructured":"Zuhair Kassem T, Wunderle M, Kuhlmann L, Ruebner M, Huebner H, Hoyer J, et al. Ex vivo chromosomal radiosensitivity testing in patients with pathological germline variants in breast cancer high-susceptibility genes BReast CAncer 1 and BReast CAncer 2. Curr Issues Mol Biol. 2023;45(8):6618\u201333. https:\/\/doi.org\/10.3390\/cimb45080418.","journal-title":"Curr Issues Mol Biol"},{"issue":"1","key":"1395_CR25","doi-asserted-by":"publisher","first-page":"105","DOI":"10.1186\/s12877-018-0799-y","volume":"18","author":"B Schuster","year":"2018","unstructured":"Schuster B, Ellmann A, Mayo T, Auer J, Haas M, Hecht M, et al. Rate of individuals with clearly increased radiosensitivity rise with age both in healthy individuals and in cancer patients. BMC Geriatr. 2018;18(1):105. https:\/\/doi.org\/10.1186\/s12877-018-0799-y.","journal-title":"BMC Geriatr"},{"key":"1395_CR26","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14010148","author":"B Schuster","year":"2021","unstructured":"Schuster B, Hecht M, Schmidt M, Haderlein M, Jost T, Buttner-Herold M, et al. Influence of gender on radiosensitivity during radiochemotherapy of advanced rectal cancer. Cancers (Basel). 2021. https:\/\/doi.org\/10.3390\/cancers14010148.","journal-title":"Cancers (Basel)"},{"issue":"6","key":"1395_CR27","doi-asserted-by":"publisher","first-page":"1238","DOI":"10.1093\/annonc\/mdv139","volume":"26","author":"M Hecht","year":"2015","unstructured":"Hecht M, Zimmer L, Loquai C, Weishaupt C, Gutzmer R, Schuster B, et al. Radiosensitization by BRAF inhibitor therapy-mechanism and frequency of toxicity in melanoma patients. Ann Oncol. 2015;26(6):1238\u201344. https:\/\/doi.org\/10.1093\/annonc\/mdv139.","journal-title":"Ann Oncol"},{"issue":"5","key":"1395_CR28","first-page":"2479","volume":"35","author":"J Linam","year":"2015","unstructured":"Linam J, Yang LX. Recent developments in radiosensitization. Anticancer Res. 2015;35(5):2479\u201385.","journal-title":"Anticancer Res"},{"issue":"2","key":"1395_CR29","doi-asserted-by":"publisher","first-page":"1728","DOI":"10.3892\/ol.2017.7523","volume":"15","author":"M Hecht","year":"2018","unstructured":"Hecht M, Harrer T, K\u00f6rber V, Sarpong EO, Moser F, Fiebig N, et al. Cytotoxic effect of Efavirenz in BxPC-3 pancreatic cancer cells is based on oxidative stress and is synergistic with ionizing radiation. Oncol Lett. 2018;15(2):1728\u201336. https:\/\/doi.org\/10.3892\/ol.2017.7523.","journal-title":"Oncol Lett"},{"issue":"1","key":"1395_CR30","doi-asserted-by":"publisher","first-page":"775","DOI":"10.1186\/s12885-020-07190-9","volume":"20","author":"V Weigert","year":"2020","unstructured":"Weigert V, Jost T, Hecht M, Knippertz I, Heinzerling L, Fietkau R, et al. PARP inhibitors combined with ionizing radiation induce different effects in melanoma cells and healthy fibroblasts. BMC Cancer. 2020;20(1):775. https:\/\/doi.org\/10.1186\/s12885-020-07190-9.","journal-title":"BMC Cancer"},{"issue":"1","key":"1395_CR31","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1186\/s12883-020-01966-z","volume":"20","author":"J Stritzelberger","year":"2020","unstructured":"Stritzelberger J, Lainer J, Gollwitzer S, Graf W, Jost T, Lang JD, et al. Ex vivo radiosensitivity is increased in non-cancer patients taking valproate. BMC Neurol. 2020;20(1):390. https:\/\/doi.org\/10.1186\/s12883-020-01966-z.","journal-title":"BMC Neurol"},{"issue":"12","key":"1395_CR32","doi-asserted-by":"publisher","first-page":"1128","DOI":"10.1007\/s00066-022-02009-x","volume":"199","author":"J Scheper","year":"2023","unstructured":"Scheper J, Hildebrand LS, Faulhaber EM, Deloch L, Gaipl US, Symank J, et al. Tumor-specific radiosensitizing effect of the ATM inhibitor AZD0156 in melanoma cells with low toxicity to healthy fibroblasts. Strahlenther Onkol. 2023;199(12):1128\u201339. https:\/\/doi.org\/10.1007\/s00066-022-02009-x.","journal-title":"Strahlenther Onkol"},{"issue":"8","key":"1395_CR33","doi-asserted-by":"publisher","first-page":"1181","DOI":"10.1586\/era.11.93","volume":"11","author":"DN Franz","year":"2011","unstructured":"Franz DN. Everolimus: an mTOR inhibitor for the treatment of tuberous sclerosis. Expert Rev Anticancer Ther. 2011;11(8):1181\u201392. https:\/\/doi.org\/10.1586\/era.11.93.","journal-title":"Expert Rev Anticancer Ther"},{"issue":"5","key":"1395_CR34","doi-asserted-by":"publisher","first-page":"289","DOI":"10.1007\/s00066-004-1200-y","volume":"180","author":"U Keller","year":"2004","unstructured":"Keller U, Kuechler A, Liehr T, Muller E, Grabenbauer G, Sauer R, et al. Impact of various parameters in detecting chromosomal aberrations by FISH to describe radiosensitivity. Strahlenther Onkol. 2004;180(5):289\u201396.","journal-title":"Strahlenther Onkol"},{"issue":"4","key":"1395_CR35","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1093\/gerona\/glq197","volume":"66","author":"H Endt","year":"2011","unstructured":"Endt H, Sprung CN, Keller U, Gaipl U, Fietkau R, Distel LV. Detailed analysis of DNA repair and senescence marker kinetics over the life span of a human fibroblast cell line. J Gerontol A Biol Sci Med Sci. 2011;66(4):367\u201375. https:\/\/doi.org\/10.1093\/gerona\/glq197.","journal-title":"J Gerontol A Biol Sci Med Sci"},{"issue":"5","key":"1395_CR36","doi-asserted-by":"publisher","first-page":"795","DOI":"10.1212\/01.wnl.0000113745.58425.ef","volume":"62","author":"A Humphrey","year":"2004","unstructured":"Humphrey A, Higgins JN, Yates JR, Bolton PF. Monozygotic twins with tuberous sclerosis discordant for the severity of developmental deficits. Neurology. 2004;62(5):795\u20138. https:\/\/doi.org\/10.1212\/01.wnl.0000113745.58425.ef.","journal-title":"Neurology"},{"issue":"15","key":"1395_CR37","doi-asserted-by":"publisher","first-page":"1829","DOI":"10.1101\/gad.1110003","volume":"17","author":"K Inoki","year":"2003","unstructured":"Inoki K, Li Y, Xu T, Guan KL. Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes Dev. 2003;17(15):1829\u201334. https:\/\/doi.org\/10.1101\/gad.1110003.","journal-title":"Genes Dev"},{"key":"1395_CR38","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.pediatrneurol.2016.03.015","volume":"60","author":"M Sahin","year":"2016","unstructured":"Sahin M, Henske EP, Manning BD, Ess KC, Bissler JJ, Klann E, et al. Advances and future directions for tuberous sclerosis complex research: recommendations from the 2015 strategic planning conference. Pediatr Neurol. 2016;60:1\u201312. https:\/\/doi.org\/10.1016\/j.pediatrneurol.2016.03.015.","journal-title":"Pediatr Neurol"},{"issue":"7","key":"1395_CR39","doi-asserted-by":"publisher","first-page":"3043","DOI":"10.1158\/0008-5472.CAN-06-4149","volume":"67","author":"Z Feng","year":"2007","unstructured":"Feng Z, Hu W, de Stanchina E, Teresky AK, Jin S, Lowe S, et al. The regulation of AMPK beta1, TSC2, and PTEN expression by p53: stress, cell and tissue specificity, and the role of these gene products in modulating the IGF-1-AKT-mTOR pathways. Cancer Res. 2007;67(7):3043\u201353. https:\/\/doi.org\/10.1158\/0008-5472.CAN-06-4149.","journal-title":"Cancer Res"},{"issue":"6","key":"1395_CR40","doi-asserted-by":"publisher","first-page":"4973","DOI":"10.1007\/s12035-017-0648-6","volume":"55","author":"ML Ferlazzo","year":"2018","unstructured":"Ferlazzo ML, Bach-Tobdji MKE, Djerad A, Sonzogni L, Devic C, Granzotto A, et al. Radiobiological characterization of tuberous sclerosis: a delay in the nucleo-shuttling of ATM may be responsible for radiosensitivity. Mol Neurobiol. 2018;55(6):4973\u201383. https:\/\/doi.org\/10.1007\/s12035-017-0648-6.","journal-title":"Mol Neurobiol"},{"key":"1395_CR41","doi-asserted-by":"publisher","DOI":"10.3390\/cancers14246141","author":"L El Nachef","year":"2022","unstructured":"El Nachef L, Berthel E, Ferlazzo ML, Le Reun E, Al-Choboq J, Restier-Verlet J, et al. Cancer and radiosensitivity syndromes: is impaired nuclear ATM kinase activity the primum movens? Cancers (Basel). 2022. https:\/\/doi.org\/10.3390\/cancers14246141.","journal-title":"Cancers (Basel)"},{"issue":"3","key":"1395_CR42","doi-asserted-by":"publisher","first-page":"394","DOI":"10.1080\/09553002.2020.1694189","volume":"96","author":"M Ferlazzo","year":"2020","unstructured":"Ferlazzo M, Berthel E, Granzotto A, Devic C, Sonzogni L, Bachelet JT, et al. Some mutations in the xeroderma pigmentosum D gene may lead to moderate but significant radiosensitivity associated with a delayed radiation-induced ATM nuclear localization. Int J Radiat Biol. 2020;96(3):394\u2013410. https:\/\/doi.org\/10.1080\/09553002.2020.1694189.","journal-title":"Int J Radiat Biol"},{"issue":"3","key":"1395_CR43","doi-asserted-by":"publisher","first-page":"1200","DOI":"10.1007\/s12035-013-8591-7","volume":"49","author":"ML Ferlazzo","year":"2014","unstructured":"Ferlazzo ML, Sonzogni L, Granzotto A, Bodgi L, Lartin O, Devic C, et al. Mutations of the Huntington\u2019s disease protein impact on the ATM-dependent signaling and repair pathways of the radiation-induced DNA double-strand breaks: corrective effect of statins and bisphosphonates. Mol Neurobiol. 2014;49(3):1200\u201311. https:\/\/doi.org\/10.1007\/s12035-013-8591-7.","journal-title":"Mol Neurobiol"},{"issue":"1","key":"1395_CR44","doi-asserted-by":"publisher","first-page":"556","DOI":"10.1007\/s12035-021-02615-3","volume":"59","author":"P Combemale","year":"2022","unstructured":"Combemale P, Sonzogni L, Devic C, Bencokova Z, Ferlazzo ML, Granzotto A, et al. Individual response to radiation of individuals with neurofibromatosis type I: role of the ATM protein and influence of statins and bisphosphonates. Mol Neurobiol. 2022;59(1):556\u201373. https:\/\/doi.org\/10.1007\/s12035-021-02615-3.","journal-title":"Mol Neurobiol"},{"issue":"1","key":"1395_CR45","doi-asserted-by":"publisher","first-page":"1148","DOI":"10.1016\/j.bbrc.2009.12.054","volume":"391","author":"H Inoue","year":"2010","unstructured":"Inoue H, Uyama T, Suzuki T, Kazami M, Hino O, Kobayashi T, et al. Phosphorylated hamartin-Hsp70 complex regulates apoptosis via mitochondrial localization. Biochem Biophys Res Commun. 2010;391(1):1148\u201353. https:\/\/doi.org\/10.1016\/j.bbrc.2009.12.054.","journal-title":"Biochem Biophys Res Commun"},{"issue":"1","key":"1395_CR46","doi-asserted-by":"publisher","first-page":"L258","DOI":"10.1152\/ajplung.00354.2005","volume":"292","author":"D Clements","year":"2007","unstructured":"Clements D, Mayer RJ, Johnson SR. Subcellular distribution of the TSC2 gene product tuberin in human airway smooth muscle cells is driven by multiple localization sequences and is cell-cycle dependent. Am J Physiol Lung Cell Mol Physiol. 2007;292(1):L258\u201366. https:\/\/doi.org\/10.1152\/ajplung.00354.2005.","journal-title":"Am J Physiol Lung Cell Mol Physiol"},{"issue":"8","key":"1395_CR47","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1080\/02841860500374513","volume":"44","author":"CN Andreassen","year":"2005","unstructured":"Andreassen CN. Can risk of radiotherapy-induced normal tissue complications be predicted from genetic profiles? Acta Oncol. 2005;44(8):801\u201315. https:\/\/doi.org\/10.1080\/02841860500374513.","journal-title":"Acta Oncol"},{"issue":"6","key":"1395_CR48","doi-asserted-by":"publisher","first-page":"1538","DOI":"10.1002\/ajmg.a.37644","volume":"170","author":"A Peron","year":"2016","unstructured":"Peron A, Vignoli A, La Briola F, Volpi A, Montanari E, Morenghi E, et al. Do patients with tuberous sclerosis complex have an increased risk for malignancies? Am J Med Genet A. 2016;170(6):1538\u201344. https:\/\/doi.org\/10.1002\/ajmg.a.37644.","journal-title":"Am J Med Genet A"},{"key":"1395_CR49","doi-asserted-by":"publisher","first-page":"1188371","DOI":"10.3389\/fonc.2023.1188371","volume":"13","author":"QY Zhu","year":"2023","unstructured":"Zhu QY, He ZM, Cao WM, Li B. The role of TSC2 in breast cancer: a literature review. Front Oncol. 2023;13:1188371. https:\/\/doi.org\/10.3389\/fonc.2023.1188371.","journal-title":"Front Oncol"}],"container-title":["Discover Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-024-01395-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s12672-024-01395-1\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s12672-024-01395-1.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T23:20:35Z","timestamp":1757114435000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s12672-024-01395-1"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,10,4]]},"references-count":49,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["1395"],"URL":"https:\/\/doi.org\/10.1007\/s12672-024-01395-1","relation":{},"ISSN":["2730-6011"],"issn-type":[{"value":"2730-6011","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,10,4]]},"assertion":[{"value":"10 July 2024","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"24 September 2024","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 October 2024","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 July 2025","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Update","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"This article has been updated to amend the license information.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"Ethical approval was obtained from the Ethics Committee of the medical faculty of Friedrich-Alexander-Universit\u00e4t Erlangen-N\u00fcrnberg (21_19 B).","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"All patients and healthy individuals gave their written informed consent to the scientific processing of their material and data.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Informed consent\u00a0"}},{"value":"All methods were carried out in accordance with relevant guidelines and regulations.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Guidelines and regulations"}},{"value":"The authors declare no competing interests.","order":5,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"525"}}