Oncogenic rearrangements of the NTRK1/NGF receptor

MA Pierotti, A Greco - Cancer letters, 2006 - Elsevier
MA Pierotti, A Greco
Cancer letters, 2006Elsevier
The NTRK1 gene encodes the high affinity receptor for Nerve Growth Factor, and its action
regulates neural development and differentiation. Deregulation of NTRK1 activity is
associated with several human disorders. Loss of function mutations causes the genetic
disease congenital insensitivity to pain with anhidrosis (CIPA). Constitutive activation of
NTRK1 has been detected in several tumor types. An autocrine loop involving NTRK1 and
NGF is associated with tumor progression in prostate carcinoma and in breast cancer. A …
The NTRK1 gene encodes the high affinity receptor for Nerve Growth Factor, and its action regulates neural development and differentiation. Deregulation of NTRK1 activity is associated with several human disorders. Loss of function mutations causes the genetic disease congenital insensitivity to pain with anhidrosis (CIPA). Constitutive activation of NTRK1 has been detected in several tumor types. An autocrine loop involving NTRK1 and NGF is associated with tumor progression in prostate carcinoma and in breast cancer. A novel alternative splicing variant with constitutive oncogenic potential has been recently described in neuroblastoma. Somatic rearrangements of NTRK1, producing chimeric oncogenes with constitutive tyrosine kinase activity, have been detected in a consistent fraction of papillary thyroid tumors. The topic of this review is a detailed analysis of the thyroid TRK oncogenes. The modalities of their activation, their mechanism of action, the contribution of activating sequences, and the molecular mechanisms underlying their generation will be discussed.
Elsevier