Abstract
Sclerosing angiomatoid nodular transformation (SANT) is a rare vascular lesion of the spleen. Although several hypotheses have been suggested, the etiopathogenesis of SANT remains unknown. It is also unclear whether SANT is a reactive or a neoplastic lesion. Since CTNNB1 (β-catenin gene) exon 3 mutations were frequently detected in some rare fibrovascular lesions, we aimed to investigate the presence of oncogenic CTNNB1 mutations in SANT cases. For this purpose, 7 cases of SANT with typical histopathological features were retrieved. First, the presence of CTNNB1 exon 3 alterations was examined with a recently described immunohistochemistry-based method. Then, the findings were confirmed with polymerase chain reaction (PCR), reverse transcription PCR (RT-PCR), and Sanger sequencing. In all cases, immunochemistry of β-catenin gave a staining pattern that was suggestive of exon 3 alteration; however, no missense mutations were found in any case at the CTNNB1 exon 3 hotspot region. Subsequently, we screened for large interstitial deletions of CTNNB1 exon 3 which revealed short PCR products in three cases. Sequencing confirmed that these cases had large interstitial deletions, resulting in loss of the entire exon 3 of CTNNB1. In the remaining four cases, loss of exon 3 was documented at the cDNA level, although genomic deletion was not identified. These results demonstrate that loss of CTNNB1 exon 3 and stabilization of β-catenin with activation of Wnt signaling pathway might have a significant role in the pathogenesis of SANT. Through this study, we provided important evidence for the neoplastic nature and pathogenesis of this disorder.
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S.U., Ö.Ö., and A.I. carried out the experiments; A.S., G.G., A.S.D., I.K., A.Ü., and A.A. selected the cases and confirmed the diagnosis of SANT; S.U. and A.A. wrote the first draft; all authors interpreted the collected data and critically reviewed the manuscript. The final version of the manuscript was read and approved by all authors.
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Uzun, S., Özcan, Ö., Işık, A. et al. Loss of CTNNB1 exon 3 in sclerosing angiomatoid nodular transformation of the spleen. Virchows Arch 479, 747–754 (2021). https://doi.org/10.1007/s00428-021-03064-y
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DOI: https://doi.org/10.1007/s00428-021-03064-y