ROS1 rearrangements, t(6q22)
ROS1 gene encodes a receptor tyrosine kinase which belongs to the insulin receptor family, with downstream signaling via the MAPK pathway through phosphorylation of RAS. Chromosomal rearrangements involving ROS1 gene (6q22) have recently been identified and described in 1–2% of patients with lung cancer. In lung cancer, ROS1 fusion partners include FIG, CD74, SLC34A2 and SDC4, which lead to oncogenic transformation and constitutive kinase activity.
Preclinical data suggest that ROS1 can be targeted by ALK inhibitors due to highly similar tyrosine kinase domains. ROS1-rearranged patients represent a unique subgroup of NSCLC patients, with a relatively good prognosis, a remarkable good outcome under different regimens of chemotherapy and high response rates to crizotinib.
References:
- Scheffler, M et al. (2015) Oncotarget. 6(12):10577-85.
- Takeuchi K, et al. (2012) Nat Med. 18:378–381.
- Bergethon K, et al. (2012) J Clin Oncol. 30:863–870.
