J Neurol Surg B Skull Base 2021; 82(S 03): e112-e113
DOI: 10.1055/s-0039-3400228
Letter to the Editor

Pathogenetic Analysis of Sinonasal Teratocarcinosarcomas Reveal Actionable β-Catenin Overexpression and a β-Catenin Mutation

Simone Minasi
1   Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University, Rome, Italy
,
Ludovica De Vincentiis
2   Department of Molecular Medicine, Sapienza University, Rome, Italy
,
Aurelio D'Ecclesia
3   Division of Maxillo-Facial Surgery, Otolaryngology and Dentistry, Hospital Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy
,
Alessandro Corsi
2   Department of Molecular Medicine, Sapienza University, Rome, Italy
,
Felice Giangaspero
1   Department of Radiological Sciences, Oncology and Anatomical Pathology, Sapienza University, Rome, Italy
› Institutsangaben

Pathogenetic Analysis of Sinonasal Teratocarcinosarcomas Reveal Beta-catenin Overexpression and an Actionable Beta-catenin Mutation

We read with great interest the article “Pathogenetic Analysis of Sinonasal Teratocarcinosarcomas Reveal Actionable β-Catenin Overexpression and a β-Catenin Mutation” by Birkeland et al.[1] In the article, the authors performed targeted exome sequencing on an index Sinonasal Teratocarcinosarcoma (SNTCS) specimen and identified an activating mutation in the β-catenin gene (CTNNB1, c.134C > T, p.S45F). In addition, they confirmed β-catenin overexpression and nuclear localization via immunohistochemistry in the index tumor and in a subsequent case. Based on their findings, the authors suggested “a role for the Wnt/β-catenin pathway in SNTCS tumorigenesis,” postulated that “this mutation is a potential genetic driver mutation and an alluring prospect for treatment using inhibitors of the Wnt/β-catenin pathway” and underlined the importance “to screen for p.S45F mutations and other mutations/aberrations in β-catenin in other teratocarcinosarcoma specimens to identify if this is a common driver mutation in these tumors.”

We recently reviewed the histological slides from a sinonasal aggressive tumor developed in a 55-year-old male. Revision of the slides and immunohistochemical analysis were diagnostic of SNTCS.[1] [2] [3] Immunohistochemical stain for β-catenin was performed but failed to reveal any nuclear staining in epithelial, mesenchymal, and neural components of the tumor. We also performed exon-3 β-catenin gene analysis by Sanger's sequencing ([Fig. 1]). As shown in the figure, no mutation was detected at the c.134 (p.S45). In addition, the analysis failed to reveal mutations also at the c.121 (p.D32), c.122 (p.S33), c.123 (p.G34), c.126 (p.S37), c.130 (p.T41), and c.133 (p.P44), along with c.134, are the most commonly mutated sites in human tumors.[4]

Zoom Image
Fig. 1 Sanger's sequencing analysis of the exon 3 of CTNNB1 in the SNTCS examined in this study. Bidirectional sequence traces do not show any mutation. The codons (and the resultant amino acids) most commonly involved in human tumorigenesis (codons 32, 33, 34, 37, 41, 44, and 45) are highlighted by boxes.

Based on our result, the c.134C > T (p.S45F) mutation does not represent a common driver mutation in SNTCS and, as a whole, the key hot spots in exon 3 of CTNNB1 are not necessarily involved in SNTCS tumorigenesis. Even though the mutation identified by Birkeland et al can provide a targetable treatment option if their patient were to suffer disease recurrence, further in-depth molecular studies are necessary to identify the critical and recurrent genetic driver events involved in the tumorigenesis of SNTCS.



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Artikel online veröffentlicht:
02. Dezember 2019

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  • References

  • 1 Birkeland AC, Burgin SJ, Yanik M. et al. Pathogenetic analysis of sinonasal teratocarcinosarcomas reveal actionable β-catenin overexpression and a β-catenin mutation. J Neurol Surg B Skull Base 2017; 78 (04) 346-352
  • 2 Fatima SS, Minhas K, Din NU, Fatima S, Ahmed A, Ahmad Z. Sinonasal teratocarcinosarcoma: a clinicopathologic and immunohistochemical study of 6 cases. Ann Diagn Pathol 2013; 17 (04) 313-318
  • 3 Franchi A, Wenig BM. Teratocarcinosarcoma. In: El-Naggar AK, Chan JKC, Grandis JR, Takata T, Slootweg PJ. eds. WHO Classification of Head and Neck Tumours. 4th ed. Lyon, France: IARC Press; 2017: 26-27
  • 4 Gao C, Wang Y, Broaddus R, Sun L, Xue F, Zhang W. Exon 3 mutations of CTNNB1 drive tumorigenesis: a review. Oncotarget 2017; 9 (04) 5492-5508