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ALK rearrangement by F.I.S.H.

ALK rearrangement by F.I.S.H.

A group of patients with non-small cell lung cancer (NSCLC) have tumors that contain an inversion in chromosome 2 that juxtaposes the 5' end of the echinoderm microtubule-associated protein-like 4 (EML4) gene with the 3' end of the anaplastic lymphoma kinase (ALK) gene, resulting in the novel fusion oncogene EML4-ALK. This fusion oncogene rearrangement is transforming both in vitro and in vivo and defines a distinct clinicopathologic subset of NSCLC.

Tumors that contain the EML4-ALK fusion oncogene or its variants are associated with specific clinical features, including never or light smoking history, younger age, and adenocarcinoma with signet ring or acinar histology. ALK gene arrangements are largely mutually exclusive with EGFR or KRAS mutations. Screening for this fusion gene in NSCLC is important, as "ALK-positive" tumors (tumors harboring a rearranged ALK gene/fusion protein) are highly sensitive to therapy with ALK-targeted inhibitors.

References:

  1. Shaw AT, Solomon B. Targeting anaplastic lymphoma kinase in lung cancer. Clin Cancer Res 2011; 17:2081.
  2. Takahashi T, Sonobe M, Kobayashi M, et al. Clinicopathologic features of non-small-cell lung cancer with EML4-ALK fusion gene. Ann Surg Oncol 2010; 17:889.
  3. Soda M, Choi YL, Enomoto M, et al. Identification of the transforming EML4-ALK fusion gene in non-small-cell lung cancer. Nature 2007; 448:561.
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F.I.S.H.