ALK gene rearrangement
ALK or Anaplastic Lymphoma receptor tyrosine Kinase is a gene located on chromosome 2p23 and is associated with Lung Cancer. The ALK gene encodes a transmembrane glycoprotein with tyrosine kinase activity. The EML4-ALK fusion is a result of an internal inversion of a small fragment of the short arm of chromosome 2 (inv(2)(p21p23)), and is detectable in up to 13% of non-small cell lung carcinomas. This fusion results in the formation of chimeric protein which helps in controlling cell proliferation.
The ALK aberrations are mutually exclusive with KRAS and EFGR mutations (with very rare exceptions). Tumors with ALK rearrangement are usually associated with no/ light smoking history, young age, and acinar morphology; they are not responsive to EGFR tyrosine kinase inhibitors and are likely to be targeted by ALK kinase inhibitors.
As per the NCCN guidelines for Non small cell lung cancer, FISH test for ALK gene rearrangement is the most recommended diagnostic method for most of the lung adenocarcinomas.1
Identification of ALK rearrangement has important role in therapy decisions. The ALK mutation status impacts the response of the patients to various drugs, for e.g. Xalkori (crizotonib).
1. NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines™). Non-Small Cell Lung Cancer (Version 3.2011). © 2011 National Comprehensive Cancer Network, Inc. Available at: NCCN.org. Accessed [March 28, 2011].
Flourescent in Situ Hybridization
Paraffin embedded tissue blocks/slides