{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,3]],"date-time":"2025-10-03T22:29:11Z","timestamp":1759530551033},"reference-count":49,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"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>Cutaneous basal cell carcinoma (cBCC) is an economic burden to health services, due to its great morbidity and increasing incidence in old people. Infiltrative cBCCs and cBCCs with micronodular pattern are considered as more aggressive. The role of p53 expression and <jats:italic>TERTp<\/jats:italic> mutation on cBCC behavior remains to be clarified. We aimed to assess <jats:italic>TERTp<\/jats:italic> mutations and p53 expression in relation to the cBCC histological subtype in a cohort of patients referred to an ENT Department of a tertiary Hospital of Northern Portugal. We performed a retrospective clinicopathological and histological review of the head and neck cBCCs followed-up at the otorhinolaryngology department of Tr\u00e1s-os-Montes e Alto Douro hospital (January 2007\u2013June 2018). We assessed <jats:italic>TERTp<\/jats:italic> mutations in 142 cBCCs and p53 protein expression, through immunohistochemistry, in 157 cBCCs. We detected <jats:italic>TERTp<\/jats:italic> mutations in 43.7% of cBCCs and p53 overexpression in 60.5% of cBCCs. We spotted association of p53 overexpression and <jats:italic>TERTp<\/jats:italic> mutation with necrosis. In the infitrative-growth pattern cBCCs, there was no significant association with the clinical and histological features evaluated, except for necrosis. In the indolent-growth cBCCs, we identified a significant association of <jats:italic>TERTp<\/jats:italic> mutation status with female sex, necrosis, multiple cBCCs, and p53 positive expression. Our results suggest that <jats:italic>TERTp<\/jats:italic> mutation may be useful to identify more aggressive features in the indolent-growth pattern cBCCs (nodular and superficial subtypes). Further studies with larger cohorts are warranted to clarify the relevance of <jats:italic>TERTp<\/jats:italic> mutation in cBCCs.<\/jats:p>","DOI":"10.1038\/s41598-021-89906-w","type":"journal-article","created":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T10:04:53Z","timestamp":1621245893000},"update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["TERTp mutations and p53 expression in head and neck cutaneous basal cell carcinomas with different aggressive features"],"prefix":"10.1038","volume":"11","author":[{"given":"Ant\u00f3nio","family":"Castanheira","sequence":"first","affiliation":[]},{"given":"Maria Jo\u00e3o","family":"Vieira","sequence":"additional","affiliation":[]},{"given":"Mafalda","family":"Pinto","sequence":"additional","affiliation":[]},{"given":"Carolina","family":"Dias","sequence":"additional","affiliation":[]},{"given":"Lu\u00edsa","family":"Prada","sequence":"additional","affiliation":[]},{"given":"Sofia","family":"Macedo","sequence":"additional","affiliation":[]},{"given":"Margarida S\u00e1","family":"Fernandes","sequence":"additional","affiliation":[]},{"given":"Fortunato","family":"Vieira","sequence":"additional","affiliation":[]},{"given":"Paula","family":"Soares","sequence":"additional","affiliation":[]},{"given":"Alberto","family":"Mota","sequence":"additional","affiliation":[]},{"given":"Jos\u00e9 Manuel","family":"Lopes","sequence":"additional","affiliation":[]},{"given":"Paula","family":"Boaventura","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2021,5,17]]},"reference":[{"issue":"22","key":"89906_CR1","doi-asserted-by":"publisher","first-page":"3011","DOI":"10.2217\/fon.15.246","volume":"11","author":"TR Correia de S\u00e1","year":"2015","unstructured":"Correia de S\u00e1, T. R., Silva, R. & Lopes, J. M. Basal cell carcinoma of the skin (part 1): epidemiology, pathology and genetic syndromes. Future Oncol. 11(22), 3011\u20133021 (2015).","journal-title":"Future Oncol."},{"key":"89906_CR2","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1016\/j.ejca.2019.06.003","volume":"118","author":"K Peris","year":"2019","unstructured":"Peris, K. et al. Diagnosis and treatment of basal cell carcinoma: European consensus\u2013based interdisciplinary guidelines. Eur. J. Cancer 118, 10\u201334 (2019).","journal-title":"Eur. J. Cancer"},{"issue":"11","key":"89906_CR3","doi-asserted-by":"publisher","first-page":"2485","DOI":"10.3390\/ijms18112485","volume":"18","author":"C Pellegrini","year":"2017","unstructured":"Pellegrini, C. et al. Understanding the molecular genetics of basal cell carcinoma. Int. J. Mol. Sci. 18(11), 2485 (2017).","journal-title":"Int. J. Mol. Sci."},{"issue":"1","key":"89906_CR4","first-page":"94","volume":"17","author":"BM Lang","year":"2019","unstructured":"Lang, B. M. et al. S2k guidelines for cutaneous basal cell carcinoma-part 1: epidemiology, genetics and diagnosis. JDDG 17(1), 94\u2013103 (2019).","journal-title":"JDDG"},{"issue":"2","key":"89906_CR5","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1111\/bjd.15321","volume":"177","author":"J Verkouteren","year":"2017","unstructured":"Verkouteren, J. et al. Epidemiology of basal cell carcinoma: scholarly review. Br. J. Dermatol. 177(2), 359\u2013372 (2017).","journal-title":"Br. J. Dermatol."},{"issue":"3","key":"89906_CR6","first-page":"0203a02","volume":"2","author":"J Pyne","year":"2012","unstructured":"Pyne, J., Sapkota, D. & Wong, J. C. Aggressive basal cell carcinoma: dermatoscopy vascular features as clues to the diagnosis. Dermatol. Pract. Concept. 2(3), 0203a02 (2012).","journal-title":"Br. J. Dermatol."},{"issue":"2","key":"89906_CR7","doi-asserted-by":"publisher","first-page":"S127","DOI":"10.1038\/modpathol.3800512","volume":"19","author":"AN Crowson","year":"2006","unstructured":"Crowson, A. N. Basal cell carcinoma: biology, morphology and clinical implications. Mod. Pathol. 19(2), S127\u2013S147 (2006).","journal-title":"Mod. Pathol."},{"issue":"2","key":"89906_CR8","first-page":"119","volume":"28","author":"UK Yal\u00e7in","year":"2012","unstructured":"Yal\u00e7in, U. K. & Se\u00e7kin, S. The expression of p53 and COX-2 in basal cell carcinoma, squamous cell carcinoma and actinic keratosis cases. Turk Patoloji Derg. 28(2), 119\u2013127 (2012).","journal-title":"Turk Patoloji Derg."},{"issue":"4","key":"89906_CR9","first-page":"1115","volume":"59","author":"AO Enache","year":"2018","unstructured":"Enache, A. O. et al. Immunoexpression of p53 and COX-2 in basal cell carcinoma. Rom. J. Morphol. Embryol. 59(4), 1115\u20131120 (2018).","journal-title":"Rom. J. Morphol. Embryol."},{"issue":"5","key":"89906_CR10","first-page":"543","volume":"16","author":"H Ansarin","year":"2006","unstructured":"Ansarin, H., Daliri, M. & Soltani-Arabshahi, R. Expression of p53 in aggressive and non-aggressive histologic variants of basal cell carcinoma. Eur. J. Dermatol. 16(5), 543\u2013547 (2006).","journal-title":"Eur. J. Dermatol."},{"issue":"6","key":"89906_CR11","doi-asserted-by":"publisher","first-page":"568","DOI":"10.1046\/j.1365-2559.2002.01393.x","volume":"40","author":"S Auepemkiate","year":"2002","unstructured":"Auepemkiate, S., Boonyaphiphat, P. & Thongsuksai, P. p53 expression related to the aggressive infiltrative histopathological feature of basal cell carcinoma. Histopathology 40(6), 568\u2013573 (2002).","journal-title":"Histopathology"},{"issue":"9","key":"89906_CR12","doi-asserted-by":"publisher","first-page":"958","DOI":"10.1111\/j.1600-0560.2009.01204.x","volume":"36","author":"RD Koseoglu","year":"2009","unstructured":"Koseoglu, R. D. et al. Expressions of p53, cyclinD1 and histopathological features in basal cell carcinomas. J. Cutan. Pathol. 36(9), 958\u2013965 (2009).","journal-title":"J. Cutan. Pathol."},{"issue":"1","key":"89906_CR13","first-page":"228","volume":"9","author":"S Bolshakov","year":"2003","unstructured":"Bolshakov, S. et al. p53 mutations in human aggressive and nonaggressive basal and squamous cell carcinomas. Clin. Cancer Res. 9(1), 228\u2013234 (2003).","journal-title":"Clin. Cancer Res."},{"issue":"4","key":"89906_CR14","doi-asserted-by":"publisher","first-page":"516","DOI":"10.1038\/modpathol.2013.167","volume":"27","author":"GA Scott","year":"2014","unstructured":"Scott, G. A., Laughlin, T. S. & Rothberg, P. G. Mutations of the TERT promoter are common in basal cell carcinoma and squamous cell carcinoma. Mod. Pathol. 27(4), 516 (2014).","journal-title":"Mod. Pathol."},{"issue":"8","key":"89906_CR15","doi-asserted-by":"publisher","first-page":"2251","DOI":"10.1038\/jid.2014.163","volume":"134","author":"H Populo","year":"2014","unstructured":"Populo, H. et al. TERT promoter mutations in skin cancer: the effects of sun exposure and X-irradiation. J. Invest. Dermatol. 134(8), 2251\u20132257 (2014).","journal-title":"J. Invest. Dermatol."},{"issue":"11","key":"89906_CR16","doi-asserted-by":"publisher","first-page":"e80354","DOI":"10.1371\/journal.pone.0080354","volume":"8","author":"KG Griewank","year":"2013","unstructured":"Griewank, K. G. et al. TERT promoter mutations are frequent in cutaneous basal cell carcinoma and squamous cell carcinoma. PLoS ONE 8(11), e80354 (2013).","journal-title":"PLoS ONE"},{"issue":"3","key":"89906_CR17","first-page":"2368","volume":"19","author":"D Lombardo","year":"2020","unstructured":"Lombardo, D. et al. Frequency of somatic mutations in TERT promoter, TP53 and CTNNB1 genes in patients with hepatocellular carcinoma from Southern Italy. Oncol. Lett. 19(3), 2368\u20132374 (2020).","journal-title":"Oncol. Lett."},{"issue":"5","key":"89906_CR18","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1101\/cshperspect.a026088","volume":"7","author":"CM Roake","year":"2017","unstructured":"Roake, C. M. & Artandi, S. E. Control of cellular aging, tissue function, and cancer by p53 downstream of telomeres. Cold Spring Harb. Perspect. Med. 7(5), 1\u201316 (2017).","journal-title":"Cold Spring Harb. Perspect. Med."},{"issue":"3","key":"89906_CR19","doi-asserted-by":"publisher","first-page":"660","DOI":"10.1016\/j.jaad.2018.08.032","volume":"80","author":"MA Campos","year":"2019","unstructured":"Campos, M. A. et al. TERT promoter mutations are associated with poor prognosis in cutaneous squamous cell carcinoma. J. Am. Acad. Dermatol. 80(3), 660\u2013669 (2019).","journal-title":"J. Am. Acad. Dermatol."},{"issue":"3","key":"89906_CR20","doi-asserted-by":"publisher","first-page":"749","DOI":"10.3390\/cells9030749","volume":"9","author":"F Hafezi","year":"2020","unstructured":"Hafezi, F. & Perez Bercoff, D. The solo play of TERT promoter mutations. Cells 9(3), 749 (2020).","journal-title":"Cells"},{"issue":"1","key":"89906_CR21","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1002\/(SICI)1096-8644(200005)112:1<17::AID-AJPA3>3.0.CO;2-D","volume":"112","author":"MD Shriver","year":"2000","unstructured":"Shriver, M. D. & Parra, E. J. Comparison of narrow-band reflectance spectroscopy and tristimulus colorimetry for measurements of skin and hair color in persons of different biological ancestry. Am J Phys Anthropol Off Publ Am Assoc Phys Anthropol 112(1), 17\u201327 (2000).","journal-title":"Am J Phys Anthropol Off Publ Am Assoc Phys Anthropol"},{"issue":"5","key":"89906_CR22","doi-asserted-by":"publisher","first-page":"393","DOI":"10.1046\/j.1365-2559.1998.00431.x","volume":"32","author":"J Rippey","year":"1998","unstructured":"Rippey, J. Why classify basal cell carcinomas?. Histopathology 32(5), 393\u2013398 (1998).","journal-title":"Histopathology"},{"issue":"3","key":"89906_CR23","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1007\/s12253-011-9363-1","volume":"17","author":"A Stamatelli","year":"2011","unstructured":"Stamatelli, A. et al. B-Raf mutations, microsatellite instability and p53 protein expression in sporadic basal cell carcinomas. Pathol Oncol Res 17(3), 633\u2013637 (2011).","journal-title":"Pathol Oncol Res"},{"issue":"4","key":"89906_CR24","first-page":"167","volume":"4","author":"RGF Haghighi","year":"2005","unstructured":"Haghighi, R. G. F. Immunohistochemistry assessment of p53 protein in basal cell carcinoma. Iran. J. Allergy Asthma Immunol. 4(4), 167\u2013171 (2005).","journal-title":"Iran. J. Allergy Asthma Immunol."},{"key":"89906_CR25","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.3389\/fgene.2019.01237","volume":"10","author":"R Batista","year":"2019","unstructured":"Batista, R. et al. Validation of a novel, sensitive and specific urine-based test for recurrence surveillance of patients with non-muscle invasive bladder cancer in a comprehensive multicenter study. Front. Genet. 10, 1237 (2019).","journal-title":"Front. Genet."},{"issue":"S2","key":"89906_CR26","doi-asserted-by":"publisher","first-page":"S125","DOI":"10.1017\/S0022215116000554","volume":"130","author":"C Newlands","year":"2016","unstructured":"Newlands, C. et al. Non-melanoma skin cancer: United Kingdom national multidisciplinary guidelines. J. Laryngol. Otol. 130(S2), S125\u2013S132 (2016).","journal-title":"J. Laryngol. Otol."},{"issue":"4","key":"89906_CR27","first-page":"222","volume":"52","author":"V Bartos","year":"2016","unstructured":"Bartos, V. & Kullova, M. Basal cell carcinoma of the skin with mixed histomorphology: a comparative study. Ceskoslov. Patol. 52(4), 222\u2013226 (2016).","journal-title":"Ceskoslov. Patol."},{"issue":"2","key":"89906_CR28","doi-asserted-by":"publisher","first-page":"136","DOI":"10.1590\/S0365-05962006000200004","volume":"18","author":"SAO Mantese","year":"2006","unstructured":"Mantese, S. A. O. et al. Carcinoma basocelular-An\u00e1lise de 300 casos observados em Uberl\u00e2ndia-MG Basal cell Carcinoma-Analysis of 300 cases observed in Uberl\u00e2ndia-MG, Brazxil. An. Bras. Dermatol. 18(2), 136\u2013142 (2006).","journal-title":"An. Bras. Dermatol."},{"issue":"1","key":"89906_CR29","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1046\/j.1365-2133.2002.04804.x","volume":"147","author":"Y Scrivener","year":"2002","unstructured":"Scrivener, Y., Grosshans, E. & Cribier, B. Variations of basal cell carcinomas according to gender, age, location and histopathological subtype. Br. J. Dermatol. 147(1), 41\u201347 (2002).","journal-title":"Br. J. Dermatol."},{"key":"89906_CR30","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2014\/858636","volume":"2014","author":"DD Demirseren","year":"2014","unstructured":"Demirseren, D. D. et al. Basal cell carcinoma of the head and neck region: a retrospective analysis of completely excised 331 cases. J. Skin Cancer. 2014, 1\u20136 (2014).","journal-title":"J. Skin Cancer"},{"issue":"6","key":"89906_CR31","doi-asserted-by":"publisher","first-page":"1118","DOI":"10.1016\/0190-9622(90)70344-H","volume":"23","author":"M Sexton","year":"1990","unstructured":"Sexton, M., Jones, D. B. & Maloney, M. E. Histologic pattern analysis of basal cell carcinoma: study of a series of 1039 consecutive neoplasms. J. Am. Acad. Dermatol. 23(6), 1118\u20131126 (1990).","journal-title":"J. Am. Acad. Dermatol."},{"issue":"1","key":"89906_CR32","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1016\/j.jdermsci.2013.09.002","volume":"73","author":"P Boaventura","year":"2014","unstructured":"Boaventura, P. et al. Mitochondrial D310 D-loop instability and histological subtypes in radiation-induced cutaneous basal cell carcinomas. J. Dermatol. Sci. 73(1), 31\u201339 (2014).","journal-title":"J. Dermatol. Sci."},{"issue":"3","key":"89906_CR33","doi-asserted-by":"publisher","first-page":"452","DOI":"10.1016\/j.jaad.2005.04.087","volume":"53","author":"I Leibovitch","year":"2005","unstructured":"Leibovitch, I. et al. Basal cell carcinoma treated with Mohs surgery in Australia II. Outcome at 5-year follow-up. J. Am. Acad. Dermatol. 53(3), 452\u2013457 (2005).","journal-title":"J. Am. Acad. Dermatol."},{"issue":"1","key":"89906_CR34","doi-asserted-by":"publisher","first-page":"56","DOI":"10.4103\/0019-5154.123496","volume":"59","author":"A Ghanadan","year":"2014","unstructured":"Ghanadan, A. et al. Characteristics of mixed type basal cell carcinoma in comparison to other BCC subtypes. Indian J. Dermatol. 59(1), 56\u201359 (2014).","journal-title":"Indian J. Dermatol."},{"issue":"5","key":"89906_CR35","doi-asserted-by":"publisher","first-page":"490","DOI":"10.1684\/ejd.2019.3643","volume":"29","author":"E Bourlidou","year":"2019","unstructured":"Bourlidou, E. et al. Risk factors for local recurrence of basal cell carcinoma and cutaneous squamous cell carcinoma of the middle third of the face: a 15-year retrospective analysis based on a single centre. Eur. J. Dermatol. 29(5), 490\u2013499 (2019).","journal-title":"Eur. J. Dermatol."},{"issue":"1","key":"89906_CR36","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1590\/S0365-05962003000100003","volume":"78","author":"AM Bandeira","year":"2003","unstructured":"Bandeira, A. M. et al. Basal cell carcinomas: anatomopathological and clinical study of 704 tumors. An. Bras. Dermatol. 78(1), 23\u201334 (2003).","journal-title":"An. Bras. Dermatol."},{"issue":"7","key":"89906_CR37","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1111\/j.1346-8138.2009.00772.x","volume":"37","author":"R Betti","year":"2010","unstructured":"Betti, R. et al. Micronodular basal cell carcinoma: a distinct subtype? Relationship with nodular and infiltrative basal cell carcinomas. J. Dermatol. 37(7), 611\u2013616 (2010).","journal-title":"J. Dermatol."},{"issue":"1","key":"89906_CR38","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.jaad.2011.02.035","volume":"67","author":"MJ Welsch","year":"2012","unstructured":"Welsch, M. J. et al. Basal cell carcinoma characteristics as predictors of depth of invasion. J. Am. Acad. Dermatol. 67(1), 47\u201353 (2012).","journal-title":"J. Am. Acad. Dermatol."},{"issue":"11","key":"89906_CR39","doi-asserted-by":"publisher","first-page":"2309","DOI":"10.1007\/s00018-016-2202-5","volume":"73","author":"Y Ying","year":"2016","unstructured":"Ying, Y. & Padanilam, B. J. Regulation of necrotic cell death: p53, PARP1 and cyclophilin D-overlapping pathways of regulated necrosis?. Cell. Mol. Life Sci. 73(11), 2309\u20132324 (2016).","journal-title":"Cell. Mol. Life Sci."},{"issue":"6","key":"89906_CR40","doi-asserted-by":"publisher","first-page":"580","DOI":"10.1097\/00000372-199612000-00005","volume":"18","author":"H Onodera","year":"1996","unstructured":"Onodera, H., Nakamura, S. & Sugai, T. Cell proliferation and p53 protein expressions in cutaneous epithelial neoplasms. Am. J. Dermatopathol. 18(6), 580\u2013588 (1996).","journal-title":"Am. J. Dermatopathol."},{"issue":"3","key":"89906_CR41","doi-asserted-by":"publisher","first-page":"279","DOI":"10.29021\/spdv.76.3.919","volume":"76","author":"MAC Campos","year":"2018","unstructured":"Campos, M. A. C. et al. Trends of cutaneous squamous cell carcinoma in the hospital of Gaia (2004\u20132013). J. Portug. Soc. Dermatol. Venereol. 76(3), 279\u2013286 (2018).","journal-title":"J. Portug. Soc. Dermatol. Venereol."},{"issue":"3","key":"89906_CR42","doi-asserted-by":"publisher","first-page":"947","DOI":"10.3390\/ijms21030947","volume":"21","author":"R Batista","year":"2020","unstructured":"Batista, R. et al. TERT promoter mutation as a potential predictive biomarker in BCG-treated bladder cancer patients. Int. J. Mol. Sci. 21(3), 947 (2020).","journal-title":"Int. J. Mol. Sci."},{"issue":"4","key":"89906_CR43","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1007\/s00428-019-02660-3","volume":"476","author":"I Machado","year":"2020","unstructured":"Machado, I. et al. Solitary fibrous tumor: a case series identifying pathological adverse factors-implications for risk stratification and classification. Virchows Arch. 476(4), 597\u2013607 (2020).","journal-title":"Virchows Arch."},{"issue":"3","key":"89906_CR44","doi-asserted-by":"publisher","first-page":"347","DOI":"10.1016\/j.humpath.2014.11.018","volume":"46","author":"K Akaike","year":"2015","unstructured":"Akaike, K. et al. Distinct clinicopathological features of NAB2-STAT6 fusion gene variants in solitary fibrous tumor with emphasis on the acquisition of highly malignant potential. Hum. Pathol. 46(3), 347\u2013356 (2015).","journal-title":"Hum. Pathol."},{"issue":"11","key":"89906_CR45","doi-asserted-by":"publisher","first-page":"R499","DOI":"10.1530\/ERC-16-0372","volume":"23","author":"V Marotta","year":"2016","unstructured":"Marotta, V. et al. Application of molecular biology of differentiated thyroid cancer for clinical prognostication. Endocr. Relat. Cancer 23(11), R499\u2013R515 (2016).","journal-title":"Endocr. Relat. Cancer"},{"issue":"4","key":"89906_CR46","doi-asserted-by":"publisher","first-page":"1726","DOI":"10.3390\/ijms22041726","volume":"22","author":"C Romei","year":"2021","unstructured":"Romei, C. & Elisei, R. A narrative review of genetic alterations in primary thyroid epithelial cancer. Int. J. Mol. Sci. 22(4), 1726\u20131741 (2021).","journal-title":"Int. J. Mol. Sci."},{"issue":"5","key":"89906_CR47","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1038\/ng.3252","volume":"47","author":"K Schulze","year":"2015","unstructured":"Schulze, K. et al. Exome sequencing of hepatocellular carcinomas identifies new mutational signatures and potential therapeutic targets. Nat. Genet. 47(5), 505\u2013511 (2015).","journal-title":"Nat. Genet."},{"issue":"2","key":"89906_CR48","doi-asserted-by":"publisher","first-page":"274","DOI":"10.1016\/j.eururo.2013.10.038","volume":"65","author":"S Wu","year":"2014","unstructured":"Wu, S. et al. Telomerase reverse transcriptase gene promoter mutations help discern the origin of urogenital tumors: a genomic and molecular study. Eur. Urol. 65(2), 274\u2013277 (2014).","journal-title":"Eur. Urol."},{"issue":"2","key":"89906_CR49","first-page":"263","volume":"55","author":"R Mercu\u0162","year":"2014","unstructured":"Mercu\u0162, R. et al. Expression of p53, D2\u201340 and \u03b1-smooth muscle actin in different histological subtypes of facial basal cell carcinoma. Rom. J. Morphol. Embryol. 55(2), 263\u2013272 (2014).","journal-title":"Rom. J. Morphol. Embryol."}],"container-title":["Scientific Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-89906-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-89906-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-89906-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,3]],"date-time":"2022-12-03T08:23:22Z","timestamp":1670055802000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41598-021-89906-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,5,17]]},"references-count":49,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["89906"],"URL":"https:\/\/doi.org\/10.1038\/s41598-021-89906-w","relation":{},"ISSN":["2045-2322"],"issn-type":[{"value":"2045-2322","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,5,17]]},"assertion":[{"value":"7 September 2020","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 May 2021","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 May 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":"10395"}}