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Alternative Signaling Mechanisms in TGCT Could Improve Diagnosis, Treatment
In a large cohort study, tenosynovial giant cell tumors (TGCTs) were found to be characterized by variable alterations, all leading to truncation of the 3′ end of CSF1 versus the COL6A3‐CSF1 fusions previously documented in certain TGCTs (Genes Chromosomes Cancer. 2020;59[2]:96-105).
Robert Maki, MD, PhD, Northwell Health Cancer Center Institute, New York, provides a brief commentary on the study and its relevance to the diagnosis and treatment of patients with TGCT.
This important paper provides data that the reciprocal translocation to that believed to be the driver alteration in TGCT (ie, COL6A3-CSF1) may actually be the less important of the 2 fusion genes when a reciprocal translocation is formed.
The investigators found that rearrangements in the CSF1 3’ (downstream) region of the gene were more consistently seen than COL6A3-CSF1 alterations, and all were downstream of exon 5, suggesting that the reason for TGCT forming is the overexpression by disinhibition (by deletion of the 3’ region) of the CSF1 gene.
These data are the strongest provided to date the alternative means of CSF1 expression other than a COL6A3-CSF1 translocation are critical to the development of TGCT. Instead, disinhibition of the CSF1 gene by deletion of its 3’ end may allow for expression of the gene and development of the inflammatory infiltrate characteristic of TGCT.
These are very important data, because this information both may lead to more accurate diagnostic tools to identify TGCT, and lead to better therapeutics for the diagnosis.
