PARS2

Overview

PARS2 encodes prolyl-tRNA synthetase 2, a mitochondrial aminoacyl-tRNA synthetase. It is notable in cancer genomics as a fusion partner generating PARS2-NOTCH2 rearrangements, which represent a functionally distinct class of NOTCH fusions predicted to be insensitive to gamma-secretase inhibitors.

Alterations observed in the corpus

  • PARS2-NOTCH2 fusion identified in the MET500 pan-cancer metastatic cohort (n=500); this fusion class is predicted to be gamma-secretase-inhibitor-independent (contrast with NOTCH2-SPAG17 fusions which are gamma-secretase-sensitive), guiding differential therapy selection among NOTCH-fusion-positive tumors PMID:28783718

Cancer types (linked)

Co-occurrence and mutual exclusivity

Therapeutic relevance

  • PARS2-NOTCH2 fusions are predicted gamma-secretase-inhibitor-insensitive, in contrast to NOTCH2-SPAG17 class fusions; subclassification of NOTCH fusions is necessary before selecting gamma-secretase inhibitor therapy PMID:28783718

Open questions

  • The specific cancer type(s) in which PARS2-NOTCH2 fusions arise within the MET500 cohort are not specified; functional validation of the predicted gamma-secretase insensitivity is pending.

Sources

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