TH
Overview
TH (Tyrosine Hydroxylase) encodes the rate-limiting enzyme in catecholamine biosynthesis, converting tyrosine to L-DOPA. It is the canonical marker of noradrenergic/dopaminergic neurons and chromaffin cells. In neuroblastoma, TH expression marks NOR tumor clusters and differentiated chromaffin populations, and is a key discriminating marker for assessing tumor differentiation status.
Alterations observed in the corpus
- TH is significantly over-expressed in noradrenergic (NOR) tumor clusters (nC5/nC7/nC8/nC9) of neuroblastoma (FDR <0.01, Welch’s t-test), as part of the noradrenergic/adrenergic panel alongside PHOX2A, PHOX2B, DBH, PNMT, and ISL1. RNAscope in situ hybridization in a MYCN-amplified high-risk tumor (K10) showed TH+/MYCN+/NTRK1+/NTRK2− cells with enlarged nuclei (possibly differentiating) surrounded by small-nucleus NTRK2+ undifferentiated cells. A low-risk 4S tumor (K6) was homogeneously TH+/NTRK1+/NTRK2−. PMID:34493726
Cancer types (linked)
- NBL — TH marks chromaffin/NOR clusters enriched in low-risk neuroblastoma; its expression is used alongside RNAscope to stratify tumor cell populations between the noradrenergic (favorable) and undifferentiated (unfavorable) states. TH is also expressed in postnatal adrenal chromaffin cells (hC4) and is mutually exclusive from hC1 progenitor cells. PMID:34493726
Co-occurrence and mutual exclusivity
Therapeutic relevance
- TH expression marks well-differentiated neuroblastoma; its absence helps identify undifferentiated high-risk cells. No direct targeted therapy is reported in the corpus.
Open questions
- Whether a TH-based differentiation assay could be used to monitor therapeutic response to differentiation-inducing agents in neuroblastoma is not explored. PMID:34493726
Sources
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