TERT Promoter C228T and C250T Hotspot Mutations Are Absent in BRAF V600E‐Positive Langerhans Cell Histiocytosis
ABSTRACT Background In various malignancies, the co‐occurrence of BRAF V600E and TERT promoter mutations (C228T and C250T) has been associated with tumor aggressiveness and poor prognosis. However, the presence of these TERT promoter mutations in Langerhans cell histiocytosis (LCH) remains unexplore...
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| Format: | Article |
| Language: | English |
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Wiley
2025-08-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.71115 |
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| author | Abdou Malik Da Silva Zofia Hélias‐Rodzewicz Irena Ungureanu Jean‐François Emile |
| author_facet | Abdou Malik Da Silva Zofia Hélias‐Rodzewicz Irena Ungureanu Jean‐François Emile |
| author_sort | Abdou Malik Da Silva |
| collection | DOAJ |
| description | ABSTRACT Background In various malignancies, the co‐occurrence of BRAF V600E and TERT promoter mutations (C228T and C250T) has been associated with tumor aggressiveness and poor prognosis. However, the presence of these TERT promoter mutations in Langerhans cell histiocytosis (LCH) remains unexplored. Methods We investigated the prevalence of TERT promoter C228T and C250T mutations in 40 formalin‐fixed, paraffin‐embedded (FFPE) LCH samples positive for BRAF V600E. A nested PCR approach followed by Sanger sequencing, complemented by NGS, was used for mutation screening. Results The variant allele frequency (VAF) of BRAF V600E in the analyzed samples ranged from 0.1% to 33.6%, with a median of 17%, and 33 of 40 successfully amplified LCH samples did not harbor TERT C228T or C250T mutations. Conclusion Our findings indicate that LCH BRAF V600E‐positive samples lack the TERT promoter C228T and C250T hotspot mutations. This suggests that TERT promoter mutations may not play a significant role in LCH pathogenesis. |
| format | Article |
| id | doaj-art-5544f84ea4224a45a8fb97a63005c8d1 |
| institution | DOAJ |
| issn | 2045-7634 |
| language | English |
| publishDate | 2025-08-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj-art-5544f84ea4224a45a8fb97a63005c8d12025-08-20T03:06:40ZengWileyCancer Medicine2045-76342025-08-011415n/an/a10.1002/cam4.71115TERT Promoter C228T and C250T Hotspot Mutations Are Absent in BRAF V600E‐Positive Langerhans Cell HistiocytosisAbdou Malik Da Silva0Zofia Hélias‐Rodzewicz1Irena Ungureanu2Jean‐François Emile3Paris‐Saclay University, Versailles SQY University, EA4340‐BECCOH, Assistance Publique–Hôpitaux de Paris (AP‐HP), Ambroise‐Paré Hospital, Smart Imaging, Service de Pathologie Boulogne FranceParis‐Saclay University, Versailles SQY University, EA4340‐BECCOH, Assistance Publique–Hôpitaux de Paris (AP‐HP), Ambroise‐Paré Hospital, Smart Imaging, Service de Pathologie Boulogne FranceParis‐Saclay University, Versailles SQY University, EA4340‐BECCOH, Assistance Publique–Hôpitaux de Paris (AP‐HP), Ambroise‐Paré Hospital, Smart Imaging, Service de Pathologie Boulogne FranceParis‐Saclay University, Versailles SQY University, EA4340‐BECCOH, Assistance Publique–Hôpitaux de Paris (AP‐HP), Ambroise‐Paré Hospital, Smart Imaging, Service de Pathologie Boulogne FranceABSTRACT Background In various malignancies, the co‐occurrence of BRAF V600E and TERT promoter mutations (C228T and C250T) has been associated with tumor aggressiveness and poor prognosis. However, the presence of these TERT promoter mutations in Langerhans cell histiocytosis (LCH) remains unexplored. Methods We investigated the prevalence of TERT promoter C228T and C250T mutations in 40 formalin‐fixed, paraffin‐embedded (FFPE) LCH samples positive for BRAF V600E. A nested PCR approach followed by Sanger sequencing, complemented by NGS, was used for mutation screening. Results The variant allele frequency (VAF) of BRAF V600E in the analyzed samples ranged from 0.1% to 33.6%, with a median of 17%, and 33 of 40 successfully amplified LCH samples did not harbor TERT C228T or C250T mutations. Conclusion Our findings indicate that LCH BRAF V600E‐positive samples lack the TERT promoter C228T and C250T hotspot mutations. This suggests that TERT promoter mutations may not play a significant role in LCH pathogenesis.https://doi.org/10.1002/cam4.71115BRAFC228T mutationC250T mutationLangerhans cell histiocytosisTERT |
| spellingShingle | Abdou Malik Da Silva Zofia Hélias‐Rodzewicz Irena Ungureanu Jean‐François Emile TERT Promoter C228T and C250T Hotspot Mutations Are Absent in BRAF V600E‐Positive Langerhans Cell Histiocytosis Cancer Medicine BRAF C228T mutation C250T mutation Langerhans cell histiocytosis TERT |
| title | TERT Promoter C228T and C250T Hotspot Mutations Are Absent in BRAF V600E‐Positive Langerhans Cell Histiocytosis |
| title_full | TERT Promoter C228T and C250T Hotspot Mutations Are Absent in BRAF V600E‐Positive Langerhans Cell Histiocytosis |
| title_fullStr | TERT Promoter C228T and C250T Hotspot Mutations Are Absent in BRAF V600E‐Positive Langerhans Cell Histiocytosis |
| title_full_unstemmed | TERT Promoter C228T and C250T Hotspot Mutations Are Absent in BRAF V600E‐Positive Langerhans Cell Histiocytosis |
| title_short | TERT Promoter C228T and C250T Hotspot Mutations Are Absent in BRAF V600E‐Positive Langerhans Cell Histiocytosis |
| title_sort | tert promoter c228t and c250t hotspot mutations are absent in braf v600e positive langerhans cell histiocytosis |
| topic | BRAF C228T mutation C250T mutation Langerhans cell histiocytosis TERT |
| url | https://doi.org/10.1002/cam4.71115 |
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