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Transition from malignant schwannoma to malignant triton tumor is analyzed in a case report on a patient with recurring cancers and suspected familial predisposition. It is hypothesized that rhabdomyoblastic differentiation, which distinguishes triton from schwannoma, might be attributable to Hedgehog-Patched pathway malfunctioning. Loss of one Patched gene allele was found in the tissue of advanced triton, but the retained allele had no exon or promoter mutations. Protein levels at early cancer stages indicated possible Patched response to the pathway activation in the first occurrence of triton tumor. Later, in the recurring triton, Patched expression was several times lower than in the control tissue, suggesting that haploinsufficiency was aided by silencing of the remaining allele, although its promoter was not hypermethylated. These findings may justify further investigation of the Hedgehog- Patched pathway role in triton malignancies, especially because of the recent research on the therapeutical potential of the pathway

Hedgehog-Patched pathway aberrations in a malignant triton tumor case study