{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T05:43:54Z","timestamp":1778305434806,"version":"3.51.4"},"reference-count":59,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2016,2,17]],"date-time":"2016-02-17T00:00:00Z","timestamp":1455667200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2016,2,17]],"date-time":"2016-02-17T00:00:00Z","timestamp":1455667200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Studies using cell lines should always characterize these cells to ensure that the results are not distorted by unexpected morphological or genetic changes possibly due to culture time or passage number. Thus, the aim of this study was to describe those MIA PaCa-2 and PANC-1 cell line phenotype and genotype characteristics that may play a crucial role in pancreatic cancer therapeutic assays, namely neuroendocrine chemotherapy and peptide receptor radionuclide therapy. Epithelial, mesenchymal, endocrine and stem cell marker characterization was performed by immunohistochemistry and flow cytometry and genotyping by PCR, gene sequencing and capillary electrophoresis. MIA PaCa-2 (polymorphism) expresses CK5.6, AE1\/AE3, E-cadherin, vimentin, chromogranin A, synaptophysin, SSTR2 and NTR1 but not CD56. PANC-1 (pleomorphism) expresses CK5.6, MNF-116, vimentin, chromogranin A, CD56 and SSTR2 but not E-cadherin, synaptophysin or NTR1. MIA PaCA-1 is CD24<jats:sup>\u2212<\/jats:sup>, CD44<jats:sup>+\/++<\/jats:sup>, CD326<jats:sup>\u2212\/+<\/jats:sup> and CD133\/1<jats:sup>\u2212<\/jats:sup>, while PANC-1 is CD24<jats:sup>\u2212\/+<\/jats:sup>, CD44<jats:sup>+<\/jats:sup>, CD326<jats:sup>\u2212\/+<\/jats:sup> and CD133\/1<jats:sup>\u2212<\/jats:sup>. Both cell lines have <jats:italic>KRAS<\/jats:italic> and <jats:italic>TP53<\/jats:italic> mutations and homozygous deletions including the first 3 exons of <jats:italic>CDKN2A\/p16<\/jats:italic><jats:sup><jats:italic>INK4A<\/jats:italic><\/jats:sup>, but no <jats:italic>SMAD4\/DPC4<\/jats:italic> mutations or microsatellite instability. Both have neuroendocrine differentiation and SSTR2 receptors, precisely the features making them suitable for the therapies we propose to assay in future studies.<\/jats:p>","DOI":"10.1038\/srep21648","type":"journal-article","created":{"date-parts":[[2016,2,17]],"date-time":"2016-02-17T11:38:58Z","timestamp":1455709138000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":151,"title":["MIA PaCa-2 and PANC-1 \u2013 pancreas ductal adenocarcinoma cell lines with neuroendocrine differentiation and somatostatin receptors"],"prefix":"10.1038","volume":"6","author":[{"given":"Rui","family":"Gradiz","sequence":"first","affiliation":[]},{"given":"Henriqueta C.","family":"Silva","sequence":"additional","affiliation":[]},{"given":"Lina","family":"Carvalho","sequence":"additional","affiliation":[]},{"given":"Maria Filomena","family":"Botelho","sequence":"additional","affiliation":[]},{"given":"Anabela","family":"Mota-Pinto","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2016,2,17]]},"reference":[{"key":"BFsrep21648_CR1","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1016\/j.pan.2014.10.001","volume":"15","author":"M Hidalgo","year":"2015","unstructured":"Hidalgo, M. et al. Addressing the challenges of pancreatic cancer: future directions for improving outcomes. Pancreatology 15, 8\u201318 (2015).","journal-title":"Pancreatology"},{"key":"BFsrep21648_CR2","doi-asserted-by":"publisher","first-page":"779","DOI":"10.1093\/annonc\/mdv001","volume":"26","author":"M Malvezzi","year":"2015","unstructured":"Malvezzi, M. et al. European cancer mortality predictions for the year 2015: does lung cancer have the highest death rate in EU women? Ann Oncol 26, 779\u2013786 (2015).","journal-title":"Ann Oncol"},{"key":"BFsrep21648_CR3","doi-asserted-by":"publisher","first-page":"5","DOI":"10.3322\/caac.21254","volume":"65","author":"RL Siegel","year":"2015","unstructured":"Siegel, R. L., Miller, K. D. & Jemal, A. Cancer statistics, 2015. CA Cancer J Clin 65, 5\u201329 (2015).","journal-title":"CA Cancer J Clin"},{"key":"BFsrep21648_CR4","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1097\/SLA.0b013e3180691579","volume":"246","author":"KY Bilimoria","year":"2007","unstructured":"Bilimoria, K. Y. et al. National failure to operate on early stage pancreatic cancer. Ann Surg 246, 173\u2013180 (2007).","journal-title":"Ann Surg"},{"key":"BFsrep21648_CR5","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1056\/NEJMra1404198","volume":"371","author":"DP Ryan","year":"2014","unstructured":"Ryan, D. P., Hong, T. S. & Bardeesy, N. Pancreatic adenocarcinoma. N Engl J Med 371, 1039\u20131049 (2014).","journal-title":"N Engl J Med"},{"key":"BFsrep21648_CR6","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1038\/nrclinonc.2015.53","volume":"12","author":"I Garrido-Laguna","year":"2015","unstructured":"Garrido-Laguna, I. & Hidalgo, M. Pancreatic cancer: from state-of-the-art treatments to promising novel therapies. Nat Rev Clin Oncol 12, 319\u2013334 (2015).","journal-title":"Nat Rev Clin Oncol"},{"key":"BFsrep21648_CR7","doi-asserted-by":"publisher","first-page":"2230","DOI":"10.1002\/1097-0142(20001201)89:11<2230::AID-CNCR11>3.0.CO;2-X","volume":"89","author":"E Tezel","year":"2000","unstructured":"Tezel, E., Nagasaka, T., Nomoto, S., Sugimoto, H. & Nakao, A. Neuroendocrine-like differentiation in patients with pancreatic carcinoma. Cancer 89, 2230\u20132236 (2000).","journal-title":"Cancer"},{"key":"BFsrep21648_CR8","first-page":"213","volume":"25","author":"S Linder","year":"2006","unstructured":"Linder, S. et al. Neuroendocrine cells in pancreatic duct adenocarcinoma: an immunohistochemical study. J Exp Clin Cancer Res 25, 213\u2013221 (2006).","journal-title":"J Exp Clin Cancer Res"},{"key":"BFsrep21648_CR9","doi-asserted-by":"publisher","first-page":"547","DOI":"10.4252\/wjsc.v7.i3.547","volume":"7","author":"CV Rao","year":"2015","unstructured":"Rao, C. V. & Mohammed, A. New insights into pancreatic cancer stem cells. World J Stem Cells 7, 547\u2013555 (2015).","journal-title":"World J Stem Cells"},{"key":"BFsrep21648_CR10","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1016\/j.canlet.2014.12.004","volume":"357","author":"HX Zhan","year":"2015","unstructured":"Zhan, H. X., Xu, J. W., Wu, D., Zhang, T. P. & Hu, S. Y. Pancreatic cancer stem cells: new insight into a stubborn disease. Cancer Lett 357, 429\u2013437 (2015).","journal-title":"Cancer Lett"},{"key":"BFsrep21648_CR11","doi-asserted-by":"publisher","first-page":"217","DOI":"10.1016\/j.pan.2015.02.011","volume":"15","author":"M Beuran","year":"2015","unstructured":"Beuran, M. et al. The epithelial to mesenchymal transition in pancreatic cancer: A systematic review. Pancreatology 15, 217\u2013225 (2015).","journal-title":"Pancreatology"},{"key":"BFsrep21648_CR12","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1097\/MPA.0b013e3181878b7f","volume":"38","author":"JM Cates","year":"2009","unstructured":"Cates, J. M. et al. Epithelial-mesenchymal transition markers in pancreatic ductal adenocarcinoma. Pancreas 38, e1\u20136 (2009).","journal-title":"Pancreas"},{"key":"BFsrep21648_CR13","first-page":"1599","volume":"27","author":"Y Zhang","year":"2012","unstructured":"Zhang, Y. et al. Epithelial mesenchymal transition correlates with CD24+CD44+ and CD133+ cells in pancreatic cancer. Oncol Rep 27, 1599\u20131605 (2012).","journal-title":"Oncol Rep"},{"key":"BFsrep21648_CR14","doi-asserted-by":"publisher","first-page":"13","DOI":"10.4132\/jptm.2014.12.26","volume":"49","author":"LD Wood","year":"2015","unstructured":"Wood, L. D. & Hruban, R. H. Genomic landscapes of pancreatic neoplasia. J Pathol Transl Med 49, 13\u201322 (2015).","journal-title":"J Pathol Transl Med"},{"key":"BFsrep21648_CR15","doi-asserted-by":"publisher","first-page":"e46002","DOI":"10.1371\/journal.pone.0046002","volume":"7","author":"L Laghi","year":"2012","unstructured":"Laghi, L. et al. Irrelevance of microsatellite instability in the epidemiology of sporadic pancreatic ductal adenocarcinoma. PLoS One 7, e46002 (2012).","journal-title":"PLoS One"},{"key":"BFsrep21648_CR16","first-page":"4264","volume":"55","author":"TA Brentnall","year":"1995","unstructured":"Brentnall, T. A. et al. Microsatellite instability and K-ras mutations associated with pancreatic adenocarcinoma and pancreatitis. Cancer Res 55, 4264\u20134267 (1995).","journal-title":"Cancer Res"},{"key":"BFsrep21648_CR17","first-page":"2536","volume":"8","author":"B Nakata","year":"2002","unstructured":"Nakata, B. et al. Prognostic value of microsatellite instability in resectable pancreatic cancer. Clin Cancer Res 8, 2536\u20132540 (2002).","journal-title":"Clin Cancer Res"},{"key":"BFsrep21648_CR18","doi-asserted-by":"publisher","first-page":"1790","DOI":"10.1001\/jama.2009.1529","volume":"302","author":"F Kastrinos","year":"2009","unstructured":"Kastrinos, F. et al. Risk of pancreatic cancer in families with Lynch syndrome. Jama 302, 1790\u20131795 (2009).","journal-title":"Jama"},{"key":"BFsrep21648_CR19","doi-asserted-by":"publisher","first-page":"401","DOI":"10.1007\/s10689-014-9726-3","volume":"13","author":"I Borelli","year":"2014","unstructured":"Borelli, I. et al. A founder MLH1 mutation in Lynch syndrome families from Piedmont, Italy, is associated with an increased risk of pancreatic tumours and diverse immunohistochemical patterns. Fam Cancer 13, 401\u2013413 (2014).","journal-title":"Fam Cancer"},{"key":"BFsrep21648_CR20","doi-asserted-by":"publisher","first-page":"2820","DOI":"10.3748\/wjg.v21.i9.2820","volume":"21","author":"MR Flanagan","year":"2015","unstructured":"Flanagan, M. R. et al. Pancreatic intraductal papillary mucinous neoplasm in a patient with Lynch syndrome. World J Gastroenterol 21, 2820\u20132825 (2015).","journal-title":"World J Gastroenterol"},{"key":"BFsrep21648_CR21","doi-asserted-by":"publisher","first-page":"375","DOI":"10.1038\/cgt.2015.32","volume":"22","author":"M Shah","year":"2015","unstructured":"Shah, M. et al. Targeted radionuclide therapies for pancreatic cancer. Cancer Gene Ther 22, 375\u2013379 (2015).","journal-title":"Cancer Gene Ther"},{"key":"BFsrep21648_CR22","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1016\/j.tem.2013.11.003","volume":"25","author":"M Chalabi","year":"2014","unstructured":"Chalabi, M. et al. Somatostatin analogs: does pharmacology impact antitumor efficacy? Trends Endocrinol Metab 25, 115\u2013127 (2014).","journal-title":"Trends Endocrinol Metab"},{"key":"BFsrep21648_CR23","doi-asserted-by":"publisher","first-page":"999","DOI":"10.1038\/nrd1255","volume":"2","author":"G Weckbecker","year":"2003","unstructured":"Weckbecker, G. et al. Opportunities in somatostatin research: biological, chemical and therapeutic aspects. Nat Rev Drug Discov 2, 999\u20131017 (2003).","journal-title":"Nat Rev Drug Discov"},{"key":"BFsrep21648_CR24","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1053\/j.semnuclmed.2009.10.004","volume":"40","author":"DJ Kwekkeboom","year":"2010","unstructured":"Kwekkeboom, D. J. et al. Peptide receptor radionuclide therapy in patients with gastroenteropancreatic neuroendocrine tumors. Semin Nucl Med 40, 78\u201388 (2010).","journal-title":"Semin Nucl Med"},{"key":"BFsrep21648_CR25","doi-asserted-by":"publisher","first-page":"R1","DOI":"10.1530\/EJE-14-0488","volume":"172","author":"WA van der Zwan","year":"2015","unstructured":"van der Zwan, W. A. et al. GEPNETs update: Radionuclide therapy in neuroendocrine tumors. Eur J Endocrinol 172, R1\u20138 (2015).","journal-title":"Eur J Endocrinol"},{"key":"BFsrep21648_CR26","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1097\/00000658-200006000-00008","volume":"231","author":"RA Ehlers","year":"2000","unstructured":"Ehlers, R. A. et al. Gut peptide receptor expression in human pancreatic cancers. Ann Surg 231, 838\u2013848 (2000).","journal-title":"Ann Surg"},{"key":"BFsrep21648_CR27","doi-asserted-by":"publisher","first-page":"2445","DOI":"10.1016\/j.peptides.2006.04.030","volume":"27","author":"RE Carraway","year":"2006","unstructured":"Carraway, R. E. & Plona, A. M. Involvement of neurotensin in cancer growth: evidence, mechanisms and development of diagnostic tools. Peptides 27, 2445\u20132460 (2006).","journal-title":"Peptides"},{"key":"BFsrep21648_CR28","first-page":"1649","volume":"44","author":"F Buchegger","year":"2003","unstructured":"Buchegger, F. et al. Radiolabeled neurotensin analog, 99mTc-NT-XI, evaluated in ductal pancreatic adenocarcinoma patients. J Nucl Med 44, 1649\u20131654 (2003).","journal-title":"J Nucl Med"},{"key":"BFsrep21648_CR29","first-page":"184","volume":"3","author":"Z Wu","year":"2012","unstructured":"Wu, Z., Martinez-Fong, D., Tredaniel, J. & Forgez, P. Neurotensin and its high affinity receptor 1 as a potential pharmacological target in cancer therapy. Front Endocrinol (Lausanne) 3, 184 (2012).","journal-title":"Front Endocrinol (Lausanne)"},{"key":"BFsrep21648_CR30","doi-asserted-by":"publisher","first-page":"9361","DOI":"10.1021\/jm401491e","volume":"56","author":"C Lang","year":"2013","unstructured":"Lang, C., Maschauer, S., Hubner, H., Gmeiner, P. & Prante, O. Synthesis and evaluation of a (18)F-labeled diarylpyrazole glycoconjugate for the imaging of NTS1-positive tumors. J Med Chem 56, 9361\u20139365 (2013).","journal-title":"J Med Chem"},{"key":"BFsrep21648_CR31","doi-asserted-by":"publisher","first-page":"322","DOI":"10.1093\/jnci\/90.4.322","volume":"90","author":"WE Fisher","year":"1998","unstructured":"Fisher, W. E. et al. Expression of somatostatin receptor subtype 1-5 genes in human pancreatic cancer. J Natl Cancer Inst 90, 322\u2013324 (1998).","journal-title":"J Natl Cancer Inst"},{"key":"BFsrep21648_CR32","first-page":"118","volume":"3","author":"RE Rossi","year":"2015","unstructured":"Rossi, R. E. et al. Chromogranin A as a predictor of radiological disease progression in neuroendocrine tumours. Ann Transl Med 3, 118 (2015).","journal-title":"Ann Transl Med"},{"key":"BFsrep21648_CR33","doi-asserted-by":"publisher","first-page":"305","DOI":"10.1111\/j.1365-2559.2007.02950.x","volume":"52","author":"Y Fujiyoshi","year":"2008","unstructured":"Fujiyoshi, Y. & Eimoto, T. Chromogranin A expression correlates with tumour cell type and prognosis in signet ring cell carcinoma of the stomach. Histopathology 52, 305\u2013313 (2008).","journal-title":"Histopathology"},{"key":"BFsrep21648_CR34","doi-asserted-by":"publisher","first-page":"1420","DOI":"10.1172\/JCI39104","volume":"119","author":"R Kalluri","year":"2009","unstructured":"Kalluri, R. & Weinberg, R. A. The basics of epithelial-mesenchymal transition. J Clin Invest 119, 1420\u20131428 (2009).","journal-title":"J Clin Invest"},{"key":"BFsrep21648_CR35","doi-asserted-by":"publisher","first-page":"5820","DOI":"10.1158\/0008-5472.CAN-08-2819","volume":"69","author":"T Arumugam","year":"2009","unstructured":"Arumugam, T. et al. Epithelial to mesenchymal transition contributes to drug resistance in pancreatic cancer. Cancer Res 69, 5820\u20135828 (2009).","journal-title":"Cancer Res"},{"key":"BFsrep21648_CR36","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1097\/MPA.0b013e3181c15963","volume":"39","author":"EL Deer","year":"2010","unstructured":"Deer, E. L. et al. Phenotype and genotype of pancreatic cancer cell lines. Pancreas 39, 425\u2013435 (2010).","journal-title":"Pancreas"},{"key":"BFsrep21648_CR37","doi-asserted-by":"publisher","first-page":"3903","DOI":"10.3748\/wjg.14.3903","volume":"14","author":"P Huang","year":"2008","unstructured":"Huang, P. et al. Isolation and biological analysis of tumor stem cells from pancreatic adenocarcinoma. World J Gastroenterol 14, 3903\u20133907 (2008).","journal-title":"World J Gastroenterol"},{"key":"BFsrep21648_CR38","doi-asserted-by":"publisher","first-page":"1030","DOI":"10.1158\/0008-5472.CAN-06-2030","volume":"67","author":"C Li","year":"2007","unstructured":"Li, C. et al. Identification of pancreatic cancer stem cells. Cancer Res 67, 1030\u20131037 (2007).","journal-title":"Cancer Res"},{"key":"BFsrep21648_CR39","doi-asserted-by":"publisher","first-page":"173","DOI":"10.5301\/JBM.2011.8551","volume":"26","author":"K Yang","year":"2011","unstructured":"Yang, K. et al. Is CD133 a biomarker for cancer stem cells of colorectal cancer and brain tumors? A meta-analysis. Int J Biol Markers 26, 173\u2013180 (2011).","journal-title":"Int J Biol Markers"},{"key":"BFsrep21648_CR40","doi-asserted-by":"publisher","first-page":"313","DOI":"10.1016\/j.stem.2007.06.002","volume":"1","author":"PC Hermann","year":"2007","unstructured":"Hermann, P. C. et al. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 1, 313\u2013323 (2007).","journal-title":"Cell Stem Cell"},{"key":"BFsrep21648_CR41","doi-asserted-by":"publisher","first-page":"263","DOI":"10.4174\/jkss.2011.81.4.263","volume":"81","author":"HJ Lee","year":"2011","unstructured":"Lee, H. J. et al. Significance of CD133 as a cancer stem cell markers focusing on the tumorigenicity of pancreatic cancer cell lines. J Korean Surg Soc 81, 263\u2013270 (2011).","journal-title":"J Korean Surg Soc"},{"key":"BFsrep21648_CR42","doi-asserted-by":"publisher","first-page":"428","DOI":"10.1016\/S1499-3872(11)60073-8","volume":"10","author":"HJ Wei","year":"2011","unstructured":"Wei, H. J. et al. Expression of CD44, CD24 and ESA in pancreatic adenocarcinoma cell lines varies with local microenvironment. Hepatobiliary Pancreat Dis Int 10, 428\u2013434 (2011).","journal-title":"Hepatobiliary Pancreat Dis Int"},{"key":"BFsrep21648_CR43","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1007\/978-1-62703-287-2_15","volume":"980","author":"YJ Wang","year":"2013","unstructured":"Wang, Y. J., Bailey, J. M., Rovira, M. & Leach, S. D. Sphere-forming assays for assessment of benign and malignant pancreatic stem cells. Methods Mol Biol 980, 281\u2013290 (2013).","journal-title":"Methods Mol Biol"},{"key":"BFsrep21648_CR44","doi-asserted-by":"publisher","first-page":"249","DOI":"10.1016\/j.scr.2012.08.001","volume":"9","author":"KR Jaiswal","year":"2012","unstructured":"Jaiswal, K. R. et al. Comparative testing of various pancreatic cancer stem cells results in a novel class of pancreatic-cancer-initiating cells. Stem Cell Res 9, 249\u2013260 (2012).","journal-title":"Stem Cell Res"},{"key":"BFsrep21648_CR45","doi-asserted-by":"publisher","first-page":"283","DOI":"10.1016\/j.ccr.2012.03.003","volume":"21","author":"JA Magee","year":"2012","unstructured":"Magee, J. A., Piskounova, E. & Morrison, S. J. Cancer stem cells: impact, heterogeneity and uncertainty. Cancer Cell 21, 283\u2013296 (2012).","journal-title":"Cancer Cell"},{"key":"BFsrep21648_CR46","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jbior.2014.04.002","volume":"55","author":"O Maertens","year":"2014","unstructured":"Maertens, O. & Cichowski, K. An expanding role for RAS GTPase activating proteins (RAS GAPs) in cancer. Adv Biol Regul 55, 1\u201314 (2014).","journal-title":"Adv Biol Regul"},{"key":"BFsrep21648_CR47","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.jbior.2015.06.003","volume":"59","author":"TL Fitzgerald","year":"2015","unstructured":"Fitzgerald, T. L. et al. Roles of EGFR and KRAS and their downstream signaling pathways in pancreatic cancer and pancreatic cancer stem cells. Advances in Biological Regulation 59, 65\u201381 (2015).","journal-title":"Advances in Biological Regulation"},{"key":"BFsrep21648_CR48","doi-asserted-by":"publisher","first-page":"150960","DOI":"10.1155\/2010\/150960","volume":"2010","author":"S Jancik","year":"2010","unstructured":"Jancik, S., Drabek, J., Radzioch, D. & Hajduch, M. Clinical relevance of KRAS in human cancers. J Biomed Biotechnol 2010, 150960 (2010).","journal-title":"J Biomed Biotechnol"},{"key":"BFsrep21648_CR49","doi-asserted-by":"publisher","first-page":"4888","DOI":"10.2174\/09298673113206660262","volume":"20","author":"NS Moorthy","year":"2013","unstructured":"Moorthy, N. S., Sousa, S. F., Ramos, M. J. & Fernandes, P. A. Farnesyltransferase inhibitors: a comprehensive review based on quantitative structural analysis. Curr Med Chem 20, 4888\u20134923 (2013).","journal-title":"Curr Med Chem"},{"key":"BFsrep21648_CR50","doi-asserted-by":"publisher","first-page":"362","DOI":"10.1136\/jmedgenet-2011-100563","volume":"49","author":"F Harinck","year":"2012","unstructured":"Harinck, F. et al. Indication for CDKN2A-mutation analysis in familial pancreatic cancer families without melanomas. J Med Genet 49, 362\u2013365 (2012).","journal-title":"J Med Genet"},{"key":"BFsrep21648_CR51","doi-asserted-by":"publisher","first-page":"472","DOI":"10.1038\/ejhg.2010.198","volume":"19","author":"RR McWilliams","year":"2011","unstructured":"McWilliams, R. R. et al. Prevalence of CDKN2A mutations in pancreatic cancer patients: implications for genetic counseling. Eur J Hum Genet 19, 472\u2013478 (2011).","journal-title":"Eur J Hum Genet"},{"key":"BFsrep21648_CR52","doi-asserted-by":"publisher","first-page":"168","DOI":"10.1309\/AJCP0FKDP7ENVKEV","volume":"141","author":"MD Reid","year":"2014","unstructured":"Reid, M. D., Saka, B., Balci, S., Goldblum, A. S. & Adsay, N. V. Molecular genetics of pancreatic neoplasms and their morphologic correlates: an update on recent advances and potential diagnostic applications. Am J Clin Pathol 141, 168\u2013180 (2014).","journal-title":"Am J Clin Pathol"},{"key":"BFsrep21648_CR53","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1038\/ng1093","volume":"33","author":"P Dumont","year":"2003","unstructured":"Dumont, P., Leu, J. I., Della Pietra, A. C. 3rd, George, D. L. & Murphy, M. The codon 72 polymorphic variants of p53 have markedly different apoptotic potential. Nat Genet 33, 357\u2013365 (2003).","journal-title":"Nat Genet"},{"key":"BFsrep21648_CR54","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1177\/1947601911408889","volume":"2","author":"N Rivlin","year":"2011","unstructured":"Rivlin, N., Brosh, R., Oren, M. & Rotter, V. Mutations in the p53 Tumor Suppressor Gene: Important Milestones at the Various Steps of Tumorigenesis. Genes Cancer 2, 466\u2013474 (2011).","journal-title":"Genes Cancer"},{"key":"BFsrep21648_CR55","doi-asserted-by":"publisher","first-page":"a001008","DOI":"10.1101\/cshperspect.a001008","volume":"2","author":"M Olivier","year":"2010","unstructured":"Olivier, M., Hollstein, M. & Hainaut, P. TP53 mutations in human cancers: origins, consequences and clinical use. Cold Spring Harb Perspect Biol 2, a001008 (2010).","journal-title":"Cold Spring Harb Perspect Biol"},{"key":"BFsrep21648_CR56","doi-asserted-by":"publisher","first-page":"861","DOI":"10.1016\/j.cell.2004.11.006","volume":"119","author":"GA Lang","year":"2004","unstructured":"Lang, G. A. et al. Gain of function of a p53 hot spot mutation in a mouse model of Li-Fraumeni syndrome. Cell 119, 861\u2013872 (2004).","journal-title":"Cell"},{"key":"BFsrep21648_CR57","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.yexcr.2014.07.004","volume":"329","author":"D Guillotin","year":"2014","unstructured":"Guillotin, D. & Martin, S. A. Exploiting DNA mismatch repair deficiency as a therapeutic strategy. Exp Cell Res 329, 110\u2013115 (2014).","journal-title":"Exp Cell Res"},{"key":"BFsrep21648_CR58","doi-asserted-by":"publisher","first-page":"4230","DOI":"10.3748\/wjg.v20.i15.4230","volume":"20","author":"JH Kim","year":"2014","unstructured":"Kim, J. H. & Kang, G. H. Molecular and prognostic heterogeneity of microsatellite-unstable colorectal cancer. World J Gastroenterol 20, 4230\u20134243 (2014).","journal-title":"World J Gastroenterol"},{"key":"BFsrep21648_CR59","doi-asserted-by":"publisher","first-page":"1804","DOI":"10.1053\/gast.2002.37070","volume":"123","author":"N Suraweera","year":"2002","unstructured":"Suraweera, N. et al. Evaluation of tumor microsatellite instability using five quasimonomorphic mononucleotide repeats and pentaplex PCR. Gastroenterology 123, 1804\u20131811 (2002).","journal-title":"Gastroenterology"}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/srep21648","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep21648.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/srep21648.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,1,4]],"date-time":"2023-01-04T14:38:07Z","timestamp":1672843087000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/srep21648"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,2,17]]},"references-count":59,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2016,4,20]]}},"alternative-id":["BFsrep21648"],"URL":"https:\/\/doi.org\/10.1038\/srep21648","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,2,17]]},"assertion":[{"value":"7 October 2015","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 January 2016","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 February 2016","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"21648"}}