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TERT promoter mutation in sebaceous neoplasms

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Abstract

TERT promoter (TERTp) mutations widely occur in multiple human neoplasms, and they have been related to different clinicopathological features. To date, this mutation has not been identified in sebaceous tumors. Here, we analyzed TERTp mutations in 91 sebaceous neoplasms (17 adenomas, 45 sebaceomas, and 29 carcinomas). We detected mutations in 26.7% (8 of 29) of sebaceous carcinomas by pyrosequencing and Sanger sequencing. No mutation was detected in adenomas or sebaceomas. The difference was significant between sebaceoma and carcinoma. The most frequent TERTp mutations were C228T and C250T in 37.5% (3 of 8) of mutated cases each one. The mutation was not associated with poor clinical evolution. Using NGS, 20 of 29 (68.5%) sebaceous carcinomas harbored mutations in 8 of the 30 genes analyzed (TP53, TERTp, EGFR, ATRX, PDGFRA, CDKN2A, PTEN, and ACVR1). With immunohistochemistry, only 1 of 8 (12.5%) TERTp-mutated carcinomas lacked mismatch repair (MMR) protein expression compared to 6 of 21 (31.6%) of non-mutated ones. Sebaceous carcinomas with MMR protein expression had significantly higher frequency of total mutations and TP53 and TERTp mutations than MMR protein-deficient carcinomas. In conclusion, TERTp mutation has been detected in sebaceous carcinomas, and its presence could be useful to differentiate sebaceous carcinoma from sebaceoma, a difficult histopathological challenge.

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All data generated or analyzed during this study are included in this published article and its supplementary information file.

References

  1. Flux K (2017) Sebaceous neoplasms. Surg Pathol Clin 10(2):367–382

    Article  Google Scholar 

  2. Wick MR, Cree IA, Kazakov DV et al (2018) Tumours with sebaceous differentiation. In: Elder ED, Massi D, Scolyer RA, Willemze R (eds) WHO classification of skin tumours, 4th edn. IARC, Lyon, pp 211–215

    Google Scholar 

  3. Tetzlaff MT, Singh RR, Seviour EG, Curry JL, Hudgens CW, Bell D, Wimmer DA, Ning J, Czerniak BA, Zhang L, Davies MA, Prieto VG, Broaddus RR, Ram P, Luthra R, Esmaeli B (2016) Next-generation sequencing identifies high frequency of mutations in potentially clinically actionable genes in sebaceous carcinoma. J Pathol 240(1):84–95

    Article  CAS  Google Scholar 

  4. Harvey NT, Tabone T, Erber W, Wood BA (2016) Circumscribed sebaceous neoplasms: a morphological, immunohistochemical and molecular analysis. Pathology. 48(5):454–462

    Article  Google Scholar 

  5. John AM, Schwartz RA (2016) Muir-Torre syndrome (MTS): an update and approach to diagnosis and management. J Am Acad Dermatol 74(3):558–566

    Article  Google Scholar 

  6. Horn S, Figl A, Rachakonda PS, Fischer C, Sucker A, Gast A, Kadel S, Moll I, Nagore E, Hemminki K, Schadendorf D, Kumar R (2013) TERT promoter mutations in familial and sporadic melanoma. Science. 339(6122):959–961

    Article  CAS  Google Scholar 

  7. Huang FW, Hodis E, Xu MJ, Kryukov GV, Chin L, Garraway LA (2013) Highly recurrent TERT promoter mutations in human melanoma. Science. 339(6122):957–959

    Article  CAS  Google Scholar 

  8. Griewank KG, Murali R, Schilling B, Schimming T, Möller I, Moll I, Schwamborn M, Sucker A, Zimmer L, Schadendorf D, Hillen U (2013) TERT promoter mutations are frequent in cutaneous basal cell carcinoma and squamous cell carcinoma. PLoS One 8(11):e80354

    Article  Google Scholar 

  9. Lin SY, Liao SL, Hong JB, Chu CY, Sheen YS, Jhuang JY, Tsai JH, Liau JY (2016) TERT promoter mutations in periocular carcinomas: implications of ultraviolet light in pathogenesis. Br J Ophthalmol 100(2):274–277

    Article  Google Scholar 

  10. Labussière M, Di Stefano AL, Gleize V et al (2014) TERT promoter mutations in gliomas, genetic associations and clinico-pathological correlations. Br J Cancer 111(10):2024–2032

    Article  Google Scholar 

  11. Kinde I, Munari E, Faraj SF, Hruban RH, Schoenberg M, Bivalacqua T, Allaf M, Springer S, Wang Y, Diaz LA Jr, Kinzler KW, Vogelstein B, Papadopoulos N, Netto GJ (2013) TERT promoter mutations occur early in urothelial neoplasia and are biomarkers of early disease and disease recurrence in urine. Cancer Res 73(24):7162–7167

    Article  CAS  Google Scholar 

  12. Liu R, Xing M (2016) TERT promoter mutations in thyroid cancer. Endocr Relat Cancer 23(3):R143–R155

    Article  CAS  Google Scholar 

  13. Quaas A, Oldopp T, Tharun L, Klingenfeld C, Krech T, Sauter G, Grob TJ (2014) Frequency of TERT promoter mutations in primary tumors of the liver. Virchows Arch 465(6):673–677

    Article  CAS  Google Scholar 

  14. Griewank KG, Schilling B, Murali R, Bielefeld N, Schwamborn M, Sucker A, Zimmer L, Hillen U, Schaller J, Brenn T, Schadendorf D, Mentzel T (2014) TERT promoter mutations are frequent in atypical fibroxanthomas and pleomorphic dermal sarcomas. Mod Pathol 27(4):502–508

    Article  CAS  Google Scholar 

  15. D’Haene N, Meléndez B, Blanchard O, de Nève N, Lebrun L, van Campenhout C, Salmon I (2019) Design and validation of a gene-targeted, next-generation sequencing panel for routine diagnosis in gliomas. Cancers (Basel) 11(6):773

    Article  Google Scholar 

  16. Cantero D, Mollejo M, Sepúlveda JM et al (2020) TP53, ATRX alterations, and low tumor mutation load feature IDH-wildtype giant cell glioblastoma despite exceptional ultra-mutated tumors. Neurooncol Adv 2(1):vdz059

    PubMed  PubMed Central  Google Scholar 

  17. R Core Team (2018) R: a language and environment for statistical computing. R Foundation for Statistical Computing, Vienna Available at: https://www.R-project.org/

    Google Scholar 

  18. Colebatch AJ, Dobrovic A, Cooper WA (2019) TERT gene: its function and dysregulation in cancer. J Clin Pathol 72(4):281–284

    Article  CAS  Google Scholar 

  19. Hodis E, Watson IR, Kryukov GV, Arold ST, Imielinski M, Theurillat JP, Nickerson E, Auclair D, Li L, Place C, DiCara D, Ramos AH, Lawrence MS, Cibulskis K, Sivachenko A, Voet D, Saksena G, Stransky N, Onofrio RC, Winckler W, Ardlie K, Wagle N, Wargo J, Chong K, Morton DL, Stemke-Hale K, Chen G, Noble M, Meyerson M, Ladbury JE, Davies MA, Gershenwald JE, Wagner SN, Hoon DSB, Schadendorf D, Lander ES, Gabriel SB, Getz G, Garraway LA, Chin L (2012 Jul 20) A landscape of driver mutations in melanoma. Cell. 150(2):251–263

    Article  CAS  Google Scholar 

  20. Heidenreich B, Kumar R (2017) TERT promoter mutations in telomere biology. Mutat Res 771:15–31

    Article  CAS  Google Scholar 

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Acknowledgements

We acknowledge Dr. Isabelle Salmon, Dr. Nicky D’Heane, and Dr. Bárbara Meléndez from the Department of Pathology, Erasme Hospital, Université Libre de Bruxelles (ULB), Brussels, Belgium, for generously providing the NGS panel.

Funding

No funding was received for conducting this study.

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Author notes

  1. María Concepción Garrido and José-Luis Rodríguez-Peralto contributed equally to this work.

Authors and Affiliations

  1. Department of Pathology, Medical School, Universidad Complutense, Instituto i+12, Hospital Universitario 12 de Octubre, CIBERONC, Madrid, Spain

    María-Teresa Muñoz-Jiménez, Leyla Blanco, Yolanda Ruano, Erika Riveiro-Falkenbach, María Concepción Garrido & José-Luis Rodríguez-Peralto

  2. Department of Pathology, Hospital Universitario Ramón y Cajal, Madrid, Spain

    Rosario Carrillo

  3. Department of Pathology, Complejo Asistencial Universitario de Salamanca, Salamanca, Spain

    Ángel Santos-Briz

  4. Department of Dermatology, Fundación Jiménez Díaz, Madrid, Spain

    Luis Requena

  5. Dermatopathology Department, Dermatopathologie Friedrichshafen, Friedrichshafen, Germany

    Heinz Kutzner

Authors
  1. María-Teresa Muñoz-Jiménez
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  2. Leyla Blanco
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  9. María Concepción Garrido
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Contributions

Conceptualization: María-Teresa Muñoz-Jiménez, Erika Riveiro-Falkenbach, José-Luis Rodríguez-Peralto, María Concepción Garrido; methodology: Leyla Blanco, Yolanda Ruano, María-Teresa Muñoz-Jiménez, Erika Riveiro-Falkenbach, José-Luis Rodríguez-Peralto, María Concepción Garrido; formal analysis and investigation: Leyla Blanco, Yolanda Ruano, María-Teresa Muñoz-Jiménez; writing—original draft preparation: María-Teresa Muñoz-Jiménez; writing—review and editing: José Luis Rodríguez-Peralto, Yolanda Ruano, María-Teresa Muñoz-Jiménez, María Concepción Garrido; resources: José-Luis Rodríguez-Peralto, María Concepción Garrido, Rosario Carrillo, Heinz Kutzner, Luis Requena, Ángel Santos-Briz; supervision: José-Luis Rodríguez-Peralto, María Concepción Garrido, Yolanda Ruano.

Corresponding author

Correspondence to José-Luis Rodríguez-Peralto.

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Muñoz-Jiménez, MT., Blanco, L., Ruano, Y. et al. TERT promoter mutation in sebaceous neoplasms. Virchows Arch 479, 551–558 (2021). https://doi.org/10.1007/s00428-021-03083-9

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  • DOI: https://doi.org/10.1007/s00428-021-03083-9

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