Silva Abdou Malik Da, Hélias-Rodzewicz Zofia, Ungureanu Irena, Emile Jean-François
Paris-Saclay University, Versailles SQY University, EA4340-BECCOH, Assistance Publique-Hôpitaux de Paris (AP-HP), Ambroise-Paré Hospital, Smart Imaging, Service de Pathologie, Boulogne, France.
Cancer Med. 2025 Aug;14(15):e71115. doi: 10.1002/cam4.71115.
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.
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.
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.
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.
在各种恶性肿瘤中，BRAF V600E和端粒酶逆转录酶（TERT）启动子突变（C228T和C250T）的同时出现与肿瘤侵袭性和不良预后相关。然而，这些TERT启动子突变在朗格汉斯细胞组织细胞增多症（LCH）中的存在情况仍未得到探索。
我们调查了40份BRAF V600E呈阳性的福尔马林固定石蜡包埋（FFPE）LCH样本中TERT启动子C228T和C250T突变的发生率。采用巢式PCR方法，随后进行桑格测序，并辅以二代测序（NGS）进行突变筛查。
分析样本中BRAF V600E的变异等位基因频率（VAF）范围为0.1%至33.6%，中位数为17%，40份成功扩增的LCH样本中有33份未携带TERT C228T或C250T突变。
我们的研究结果表明，LCH中BRAF V600E阳性样本缺乏TERT启动子C228T和C250T热点突变。这表明TERT启动子突变可能在LCH发病机制中不发挥重要作用。
