{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,8]],"date-time":"2026-01-08T18:12:11Z","timestamp":1767895931802,"version":"3.49.0"},"reference-count":43,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T00:00:00Z","timestamp":1629072000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T00:00:00Z","timestamp":1629072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100003725","name":"National Research Foundation of Korea","doi-asserted-by":"publisher","award":["NRF-2017R1D1A1B03033587"],"award-info":[{"award-number":["NRF-2017R1D1A1B03033587"]}],"id":[{"id":"10.13039\/501100003725","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003710","name":"Korea Health Industry Development Institute","doi-asserted-by":"publisher","award":["HI14C1324"],"award-info":[{"award-number":["HI14C1324"]}],"id":[{"id":"10.13039\/501100003710","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>We aimed to identify somatic genetic alterations in pure growth hormone (GH)-secreting pituitary adenomas without <jats:italic>GNAS<\/jats:italic> variants. Patients with GH-secreting pituitary adenoma who underwent transsphenoidal adenomectomy at Severance Hospital, Yonsei University College of Medicine were recruited. Somatic genetic alterations were profiled by whole-exome sequencing (WES) and targeted resequencing. WES was performed using DNA from nine GH-secreting pituitary tumors and corresponding blood samples. Absence of <jats:italic>GNAS<\/jats:italic> variant was confirmed by Sanger sequencing. For targeted resequencing of 140 fixed tissues, 48 WES-derived candidate genes and 7 GH-secreting pituitary adenoma-associated genes were included. Forty-eight genes with 59 somatic variants were identified by WES. In targeted resequencing, variants in 26 recurrent genes, including <jats:italic>MAST4, PRIM2<\/jats:italic>, <jats:italic>TNN<\/jats:italic>, <jats:italic>STARD9<\/jats:italic>, <jats:italic>DNAH11<\/jats:italic>, <jats:italic>DOCK4<\/jats:italic>, <jats:italic>GPR98<\/jats:italic>, <jats:italic>BCHE<\/jats:italic>, <jats:italic>DARS<\/jats:italic>, <jats:italic>CUBN<\/jats:italic>, <jats:italic>NGDN<\/jats:italic>, <jats:italic>PLXND1<\/jats:italic>, <jats:italic>UNC5B<\/jats:italic>, and <jats:italic>COL22A1<\/jats:italic>, were identified, but variants in previously reported genes were not detected. <jats:italic>BCHE<\/jats:italic>, <jats:italic>DARS<\/jats:italic>, <jats:italic>NGDN<\/jats:italic>, and <jats:italic>UNC5B<\/jats:italic> variants were associated with increased GH-secreting pituitary tumor biochemical activity, which was confirmed in vitro. Although recurrent point variants were rare, several somatic variants were identified in sporadic pure GH-secreting pituitary adenomas. Several somatic variants may affect pathways involved in the tumorigenesis and biochemical activities of GH-secreting pituitary adenomas.<\/jats:p>","DOI":"10.1038\/s41598-021-95829-3","type":"journal-article","created":{"date-parts":[[2021,8,16]],"date-time":"2021-08-16T10:03:52Z","timestamp":1629108232000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Novel somatic variants involved in biochemical activity of pure growth hormone-secreting pituitary adenoma without GNAS variant"],"prefix":"10.1038","volume":"11","author":[{"given":"Cheol Ryong","family":"Ku","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyeonseob","family":"Lim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang Jong","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sun Ho","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daham","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Se Hoon","family":"Kim","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mi Kyung","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8775-9877","authenticated-orcid":false,"given":"Duhee","family":"Bang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8693-9630","authenticated-orcid":false,"given":"Eun Jig","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,8,16]]},"reference":[{"issue":"11","key":"95829_CR1","doi-asserted-by":"publisher","first-page":"3189","DOI":"10.1172\/JCI39375","volume":"119","author":"S Melmed","year":"2009","unstructured":"Melmed, S. Acromegaly pathogenesis and treatment. J Clin Invest 119(11), 3189\u20133202. https:\/\/doi.org\/10.1172\/JCI39375 (2009).","journal-title":"J Clin Invest"},{"issue":"1","key":"95829_CR2","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1210\/jc.2007-1191","volume":"93","author":"OM Dekkers","year":"2008","unstructured":"Dekkers, O. M., Biermasz, N. R., Pereira, A. M., Romijn, J. A. & Vandenbroucke, J. P. Mortality in acromegaly: A metaanalysis. J. Clin. Endocrinol. Metab. 93(1), 61\u201367 (2008).","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"5","key":"95829_CR3","doi-asserted-by":"publisher","first-page":"1743","DOI":"10.1210\/jc.2006-2547","volume":"92","author":"P Maison","year":"2007","unstructured":"Maison, P., Tropeano, A., Macquin Mavier, I., Giustina, A. & Chanson, P. Impact of somatostatin analogs on the heart in acromegaly: A metaanalysis. J. Clin. Endocrinol. Metab. 92(5), 1743\u20131747 (2007).","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"11","key":"95829_CR4","doi-asserted-by":"publisher","first-page":"836","DOI":"10.1038\/nrc926","volume":"2","author":"SL Asa","year":"2002","unstructured":"Asa, S. L. & Ezzat, S. The pathogenesis of pituitary tumours. Nat. Rev. Cancer 2(11), 836\u2013849. https:\/\/doi.org\/10.1038\/nrc926 (2002).","journal-title":"Nat. Rev. Cancer"},{"key":"95829_CR5","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1159\/000079045","volume":"32","author":"RN Clayton","year":"2004","unstructured":"Clayton, R. N. & Farrell, W. E. Pituitary tumour clonality revisited. Front. Horm. Res. 32, 186\u2013204 (2004).","journal-title":"Front. Horm. Res."},{"issue":"6","key":"95829_CR6","doi-asserted-by":"publisher","first-page":"1416","DOI":"10.1210\/jcem-71-6-1416","volume":"71","author":"CA Landis","year":"1990","unstructured":"Landis, C. A. et al. Clinical characteristics of acromegalic patients whose pituitary tumors contain mutant Gs protein. J. Clin. Endocrinol. Metab. 71(6), 1416\u20131420. https:\/\/doi.org\/10.1210\/jcem-71-6-1416 (1990).","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"6236","key":"95829_CR7","doi-asserted-by":"publisher","first-page":"692","DOI":"10.1038\/340692a0","volume":"340","author":"CA Landis","year":"1989","unstructured":"Landis, C. A. et al. GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumours. Nature 340(6236), 692\u2013696. https:\/\/doi.org\/10.1038\/340692a0 (1989).","journal-title":"Nature"},{"issue":"6148","key":"95829_CR8","doi-asserted-by":"publisher","first-page":"566","DOI":"10.1038\/330566a0","volume":"330","author":"L Vallar","year":"1987","unstructured":"Vallar, L., Spada, A. & Giannattasio, G. Altered Gs and adenylate cyclase activity in human GH-secreting pituitary adenomas. Nature 330(6148), 566\u2013568. https:\/\/doi.org\/10.1038\/330566a0 (1987).","journal-title":"Nature"},{"issue":"6053","key":"95829_CR9","doi-asserted-by":"publisher","first-page":"252","DOI":"10.1126\/science.1208930","volume":"334","author":"N Makinen","year":"2011","unstructured":"Makinen, N. et al. MED12, the mediator complex subunit 12 gene, is mutated at high frequency in uterine leiomyomas. Science 334(6053), 252\u2013255. https:\/\/doi.org\/10.1126\/science.1208930 (2011).","journal-title":"Science"},{"issue":"7407","key":"95829_CR10","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1038\/nature11252","volume":"487","author":"Cancer Genome Atlas Network","year":"2012","unstructured":"Cancer Genome Atlas Network. Comprehensive molecular characterization of human colon and rectal cancer. Nature 487(7407), 330\u2013337. https:\/\/doi.org\/10.1038\/nature11252 (2012).","journal-title":"Nature"},{"issue":"10","key":"95829_CR11","doi-asserted-by":"publisher","first-page":"3918","DOI":"10.1210\/jc.2015-3129","volume":"100","author":"N Valimaki","year":"2015","unstructured":"Valimaki, N. et al. Whole-Genome sequencing of growth hormone (GH)-secreting pituitary adenomas. J. Clin. Endocrinol. Metab. 100(10), 3918\u20133927. https:\/\/doi.org\/10.1210\/jc.2015-3129 (2015).","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"4","key":"95829_CR12","doi-asserted-by":"publisher","first-page":"E796","DOI":"10.1210\/jc.2012-4028","volume":"98","author":"PJ Newey","year":"2013","unstructured":"Newey, P. J. et al. Whole-exome sequencing studies of nonfunctioning pituitary adenomas. J. Clin. Endocrinol. Metab. 98(4), E796-800. https:\/\/doi.org\/10.1210\/jc.2012-4028 (2013).","journal-title":"J. Clin. Endocrinol. Metab."},{"issue":"1","key":"95829_CR13","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1038\/ng.3166","volume":"47","author":"M Reincke","year":"2015","unstructured":"Reincke, M. et al. Mutations in the deubiquitinase gene USP8 cause Cushing\u2019s disease. Nat. Genet. 47(1), 31\u201338. https:\/\/doi.org\/10.1038\/ng.3166 (2015).","journal-title":"Nat. Genet."},{"issue":"1","key":"95829_CR14","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1002\/1097-0142(19850101)55:1<96::aid-cncr2820550116>3.0.co;2-2","volume":"55","author":"H Mori","year":"1985","unstructured":"Mori, H. et al. Growth hormone-producing pituitary adenoma with crystal-like amyloid immunohistochemically positive for growth hormone. Cancer 55(1), 96\u2013102. https:\/\/doi.org\/10.1002\/1097-0142(19850101)55:1%3c96::aid-cncr2820550116%3e3.0.co;2-2 (1985).","journal-title":"Cancer"},{"issue":"3","key":"95829_CR15","doi-asserted-by":"publisher","first-page":"363","DOI":"10.1530\/EJE-15-1064","volume":"174","author":"CL Ronchi","year":"2016","unstructured":"Ronchi, C. L. et al. Landscape of somatic mutations in sporadic GH-secreting pituitary adenomas. Eur. J. Endocrinol. 174(3), 363\u2013372. https:\/\/doi.org\/10.1530\/EJE-15-1064 (2016).","journal-title":"Eur. J. Endocrinol."},{"issue":"25","key":"95829_CR16","doi-asserted-by":"publisher","first-page":"2363","DOI":"10.1056\/NEJMoa1408028","volume":"371","author":"G Trivellin","year":"2014","unstructured":"Trivellin, G. et al. Gigantism and acromegaly due to Xq26 microduplications and GPR101 mutation. N. Engl. J. Med. 371(25), 2363\u20132374. https:\/\/doi.org\/10.1056\/NEJMoa1408028 (2014).","journal-title":"N. Engl. J. Med."},{"issue":"4","key":"95829_CR17","doi-asserted-by":"publisher","first-page":"1386","DOI":"10.1002\/1097-0142(19930815)72:4<1386::AID-CNCR2820720439>3.0.CO;2-J","volume":"72","author":"K Yoshimoto","year":"1993","unstructured":"Yoshimoto, K., Iwahana, H., Fukuda, A., Sano, T. & Itakura, M. Rare mutations of the Gs alpha subunit gene in human endocrine tumors. Mutation detection by polymerase chain reaction-primer-introduced restriction analysis. Cancer 72(4), 1386\u20131393 (1993).","journal-title":"Cancer"},{"issue":"6","key":"95829_CR18","doi-asserted-by":"publisher","first-page":"867","DOI":"10.1530\/eje-13-0442","volume":"169","author":"F Cai","year":"2013","unstructured":"Cai, F. et al. Screening for AIP gene mutations in a Han Chinese pituitary adenoma cohort followed by LOH analysis. Eur. J. Endocrinol. 169(6), 867\u2013884. https:\/\/doi.org\/10.1530\/eje-13-0442 (2013).","journal-title":"Eur. J. Endocrinol."},{"issue":"1","key":"95829_CR19","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1186\/s12881-018-0698-2","volume":"19","author":"M Gao","year":"2018","unstructured":"Gao, M. et al. Association between acromegaly and a single nucleotide polymorphism (rs2854744) in the IGFBP3 gene. BMC Med. Genet. 19(1), 182. https:\/\/doi.org\/10.1186\/s12881-018-0698-2 (2018).","journal-title":"BMC Med. Genet."},{"issue":"D1","key":"95829_CR20","doi-asserted-by":"publisher","first-page":"D941","DOI":"10.1093\/nar\/gky1015","volume":"47","author":"JG Tate","year":"2018","unstructured":"Tate, J. G. et al. COSMIC: The catalogue of somatic mutations in cancer. Nucleic Acids Res. 47(D1), D941\u2013D947. https:\/\/doi.org\/10.1093\/nar\/gky1015 (2018).","journal-title":"Nucleic Acids Res."},{"issue":"D1","key":"95829_CR21","doi-asserted-by":"publisher","first-page":"D835","DOI":"10.1093\/nar\/gkz972","volume":"48","author":"MJ Landrum","year":"2020","unstructured":"Landrum, M. J. et al. ClinVar: Improvements to accessing data. Nucleic Acids Res. 48(D1), D835-d844. https:\/\/doi.org\/10.1093\/nar\/gkz972 (2020).","journal-title":"Nucleic Acids Res."},{"issue":"5853","key":"95829_CR22","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1126\/science.1145720","volume":"318","author":"LD Wood","year":"2007","unstructured":"Wood, L. D. et al. The genomic landscapes of human breast and colorectal cancers. Science 318(5853), 1108\u20131113. https:\/\/doi.org\/10.1126\/science.1145720 (2007).","journal-title":"Science"},{"issue":"22","key":"95829_CR23","doi-asserted-by":"publisher","first-page":"4602","DOI":"10.1242\/dev.096024","volume":"140","author":"B Charvet","year":"2013","unstructured":"Charvet, B. et al. Knockdown of col22a1 gene in zebrafish induces a muscular dystrophy by disruption of the myotendinous junction. Development 140(22), 4602\u20134613. https:\/\/doi.org\/10.1242\/dev.096024 (2013).","journal-title":"Development"},{"issue":"5","key":"95829_CR24","doi-asserted-by":"publisher","first-page":"808","DOI":"10.1134\/S0026893306050062","volume":"40","author":"L Sun","year":"2006","unstructured":"Sun, L. et al. Identification of a novel human MAST4 gene, a new member of the microtubule associated serine-threonine kinase family. Mol. Biol. (Mosk) 40(5), 808\u2013815 (2006).","journal-title":"Mol. Biol. (Mosk)"},{"issue":"6","key":"95829_CR25","doi-asserted-by":"publisher","first-page":"2413","DOI":"10.1172\/jci78448","volume":"125","author":"A Cariboni","year":"2015","unstructured":"Cariboni, A. et al. Dysfunctional SEMA3E signaling underlies gonadotropin-releasing hormone neuron deficiency in Kallmann syndrome. J. Clin. Invest. 125(6), 2413\u20132428. https:\/\/doi.org\/10.1172\/jci78448 (2015).","journal-title":"J. Clin. Invest."},{"issue":"6","key":"95829_CR26","doi-asserted-by":"publisher","first-page":"2764","DOI":"10.1210\/endo-122-6-2764","volume":"122","author":"K Meier","year":"1988","unstructured":"Meier, K., Knepel, W. & Schofl, C. Potassium depolarization elevates cytosolic free calcium concentration in rat anterior pituitary cells through 1,4-dihydropyridine-sensitive, omega-conotoxin-insensitive calcium channels. Endocrinology 122(6), 2764\u20132770. https:\/\/doi.org\/10.1210\/endo-122-6-2764 (1988).","journal-title":"Endocrinology"},{"issue":"9","key":"95829_CR27","doi-asserted-by":"publisher","first-page":"1484","DOI":"10.1210\/mend.15.9.0694","volume":"15","author":"A Garcia","year":"2001","unstructured":"Garcia, A., Alvarez, C. V., Smith, R. G. & Dieguez, C. Regulation of Pit-1 expression by ghrelin and GHRP-6 through the GH secretagogue receptor. Mol. Endocrinol. 15(9), 1484\u20131495. https:\/\/doi.org\/10.1210\/mend.15.9.0694 (2001).","journal-title":"Mol. Endocrinol."},{"issue":"11","key":"95829_CR28","doi-asserted-by":"publisher","first-page":"5219","DOI":"10.1073\/pnas.92.11.5219","volume":"92","author":"ZP Chen","year":"1995","unstructured":"Chen, Z. P. et al. Evidence for a role of pituitary ATP receptors in the regulation of pituitary function. Proc. Natl. Acad. Sci. USA 92(11), 5219\u20135223. https:\/\/doi.org\/10.1073\/pnas.92.11.5219 (1995).","journal-title":"Proc. Natl. Acad. Sci. USA"},{"issue":"9","key":"95829_CR29","doi-asserted-by":"publisher","first-page":"1413","DOI":"10.1038\/ijo.2017.123","volume":"41","author":"VP Chen","year":"2017","unstructured":"Chen, V. P., Gao, Y., Geng, L. & Brimijoin, S. Butyrylcholinesterase regulates central ghrelin signaling and has an impact on food intake and glucose homeostasis. Int. J. Obes. (Lond.) 41(9), 1413\u20131419. https:\/\/doi.org\/10.1038\/ijo.2017.123 (2017).","journal-title":"Int. J. Obes. (Lond.)"},{"issue":"5","key":"95829_CR30","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1111\/j.1365-2826.2009.01867.x","volume":"21","author":"D Yoshida","year":"2009","unstructured":"Yoshida, D., Nomura, R. & Teramoto, A. Signalling pathway mediated by CXCR7, an alternative chemokine receptor for stromal-cell derived factor-1alpha, in AtT20 mouse adrenocorticotrophic hormone-secreting pituitary adenoma cells. J. Neuroendocrinol. 21(5), 481\u2013488. https:\/\/doi.org\/10.1111\/j.1365-2826.2009.01867.x (2009).","journal-title":"J. Neuroendocrinol."},{"key":"95829_CR31","doi-asserted-by":"publisher","first-page":"11","DOI":"10.1186\/s13045-015-0108-6","volume":"8","author":"K Chen","year":"2015","unstructured":"Chen, K. et al. High expression of neuroguidin increases the sensitivity of acute myeloid leukemia cells to chemotherapeutic drugs. J. Hematol. Oncol. 8, 11. https:\/\/doi.org\/10.1186\/s13045-015-0108-6 (2015).","journal-title":"J. Hematol. Oncol."},{"issue":"10","key":"95829_CR32","doi-asserted-by":"publisher","first-page":"874","DOI":"10.1093\/jnen\/nlx072","volume":"76","author":"TE Richardson","year":"2017","unstructured":"Richardson, T. E. et al. Aggressive behavior in silent subtype III pituitary adenomas may depend on suppression of local immune response: A whole transcriptome analysis. J. Neuropathol. Exp. Neurol. 76(10), 874\u2013882. https:\/\/doi.org\/10.1093\/jnen\/nlx072 (2017).","journal-title":"J. Neuropathol. Exp. Neurol."},{"issue":"4","key":"95829_CR33","doi-asserted-by":"publisher","first-page":"491","DOI":"10.1530\/eje-12-0864","volume":"168","author":"S Larkin","year":"2013","unstructured":"Larkin, S. et al. Granulation pattern, but not GSP or GHR mutation, is associated with clinical characteristics in somatostatin-naive patients with somatotroph adenomas. Eur. J. Endocrinol. 168(4), 491\u2013499. https:\/\/doi.org\/10.1530\/eje-12-0864 (2013).","journal-title":"Eur. J. Endocrinol."},{"issue":"5","key":"95829_CR34","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1016\/j.tem.2012.11.007","volume":"24","author":"MR Gadelha","year":"2013","unstructured":"Gadelha, M. R., Kasuki, L. & Korbonits, M. Novel pathway for somatostatin analogs in patients with acromegaly. Trends Endocrinol. Metab. 24(5), 238\u2013246. https:\/\/doi.org\/10.1016\/j.tem.2012.11.007 (2013).","journal-title":"Trends Endocrinol. Metab."},{"key":"95829_CR35","first-page":"192","volume":"71","author":"CR Ku","year":"2012","unstructured":"Ku, C. R., Kim, E. H., Oh, M. C., Lee, E. J. & Kim, S. H. Surgical and endocrinological outcomes in the treatment of growth hormone-secreting pituitary adenomas according to the shift of surgical paradigm. Neurosurgery 71, 192\u2013203 (2012).","journal-title":"Neurosurgery"},{"issue":"3","key":"95829_CR36","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1530\/eje-14-0304","volume":"171","author":"CR Ku","year":"2014","unstructured":"Ku, C. R., Hong, J. W., Kim, E. H., Kim, S. H. & Lee, E. J. Clinical predictors of GH deficiency in surgically cured acromegalic patients. Eur. J. Endocrinol. 171(3), 379\u2013387. https:\/\/doi.org\/10.1530\/eje-14-0304 (2014).","journal-title":"Eur. J. Endocrinol."},{"issue":"16","key":"95829_CR37","doi-asserted-by":"publisher","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","volume":"25","author":"H Li","year":"2009","unstructured":"Li, H. et al. The Sequence Alignment\/Map format and SAMtools. Bioinformatics 25(16), 2078\u20132079. https:\/\/doi.org\/10.1093\/bioinformatics\/btp352 (2009).","journal-title":"Bioinformatics"},{"issue":"9","key":"95829_CR38","doi-asserted-by":"publisher","first-page":"1297","DOI":"10.1101\/gr.107524.110","volume":"20","author":"A McKenna","year":"2010","unstructured":"McKenna, A. et al. The Genome Analysis Toolkit: A MapReduce framework for analyzing next-generation DNA sequencing data. Genome Res. 20(9), 1297\u20131303. https:\/\/doi.org\/10.1101\/gr.107524.110 (2010).","journal-title":"Genome Res."},{"issue":"3","key":"95829_CR39","doi-asserted-by":"publisher","first-page":"213","DOI":"10.1038\/nbt.2514","volume":"31","author":"K Cibulskis","year":"2013","unstructured":"Cibulskis, K. et al. Sensitive detection of somatic point mutations in impure and heterogeneous cancer samples. Nat. Biotechnol. 31(3), 213\u2013219. https:\/\/doi.org\/10.1038\/nbt.2514 (2013).","journal-title":"Nat. Biotechnol."},{"issue":"3","key":"95829_CR40","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1101\/gr.129684.111","volume":"22","author":"DC Koboldt","year":"2012","unstructured":"Koboldt, D. C. et al. VarScan 2: Somatic mutation and copy number alteration discovery in cancer by exome sequencing. Genome Res. 22(3), 568\u2013576. https:\/\/doi.org\/10.1101\/gr.129684.111 (2012).","journal-title":"Genome Res."},{"key":"95829_CR41","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1186\/1471-2105-14-128","volume":"14","author":"EY Chen","year":"2013","unstructured":"Chen, E. Y. et al. Enrichr: Interactive and collaborative HTML5 gene list enrichment analysis tool. BMC Bioinform. 14, 128. https:\/\/doi.org\/10.1186\/1471-2105-14-128 (2013).","journal-title":"BMC Bioinform."},{"issue":"10","key":"95829_CR42","doi-asserted-by":"publisher","first-page":"2867","DOI":"10.3390\/ijms19102867","volume":"19","author":"WK Lee","year":"2018","unstructured":"Lee, W. K. et al. Whole exome sequencing identifies a novel hedgehog-interacting protein G516R mutation in locally advanced papillary thyroid cancer. Int. J. Mol. Sci. 19(10), 2867 (2018).","journal-title":"Int. J. Mol. Sci."},{"issue":"2","key":"95829_CR43","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1677\/JOE-08-0250","volume":"199","author":"Y Lee","year":"2008","unstructured":"Lee, Y., Kim, J. M. & Lee, E. J. Functional expression of CXCR4 in somatotrophs: CXCL12 activates GH gene, GH production and secretion, and cellular proliferation. J. Endocrinol. 199(2), 191\u2013199. https:\/\/doi.org\/10.1677\/JOE-08-0250 (2008).","journal-title":"J. Endocrinol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-95829-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-95829-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-95829-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T12:35:45Z","timestamp":1670070945000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-95829-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,8,16]]},"references-count":43,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["95829"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-95829-3","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,8,16]]},"assertion":[{"value":"12 April 2021","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"21 July 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 August 2021","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"16530"}}