A recurrent gene fusion between EML4 and ALK in 6.7% of non-small cell lung cancers (NSCLCs) and NKX2-1 (TTF1, TITF1) high-level amplifications in 12% of adenocarcinomas of the lung were independently reported recently.
Although ALK gene rearrangements affect only about 4% of all lung cancers, they are more frequent in adenocarcinomas, in never or light smokers, and seem almost mutually exclusive with activating EGFR or KRAS mutations.
EML4-ALK was investigated in 266 resected primary NSCLC, including adenocarcinomas (AD), lymphoepithelioma-like carcinomas, squamous cell carcinomas, mucoepidermoid carcinomas, and adenosquamous carcinomas, by reverse transcriptase-polymerase chain reaction and was verified by sequencing.
Primary SRC of the lung is a rare subtype of adenocarcinoma, carries a worse prognosis when compared to adenocarcinoma and shares many of the recently identified clinicopathologic characteristics ascribed to EML4-ALK positive non-small cell lung cancer.
Patients with ALK rearrangements tended to be younger than those without the rearrangements, and most of the patients had little or no exposure to tobacco and had adenocarcinomas.
Target therapies against echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase fusion protein or a mutated ERBB2 (v-ERB-B avian erythroblastic leukemia viral oncogene homologue 2) present in approximately 5% and approximately 3% of the Japanese patients with adenocarcinomas, respectively, are currently under development.
The clinicopathological features of EML4-ALK-positive adenocarcinoma are reported to include its high incidence in young, non-smoking patients, tumors that show distinct solid or acinar growth patterns with or without signet-ring cell histology, and its mutually exclusive occurrence with mutations in EGFR and KRAS.
With the emergence of selective kinase inhibitors targeting epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK), there is a corresponding need to identify the subset of NSCLCs harbouring specific genetic mutations associated with sensitivity to these agents, almost all of which are found in adenocarcinomas.
ALK gene rearrangement occurs in approximately 3-5% of non-small-cell lung cancer patients, most of whom are never- or light smokers and have adenocarcinoma histology.
NSCLC with the EML4 (echinoderm microtubule-associated protein-like 4)-ALK (anaplastic lymphoma kinase) fusion gene is also more likely to occur in never smokers and in those with adenocarcinoma histology, and is expected to benefit from ALK inhibitors.
Association of EGFR mutation or ALK rearrangement with expression of DNA repair and synthesis genes in never-smoker women with pulmonary adenocarcinoma.
Previous studies have revealed that EGFR mutation and/or EML4-ALK gene fusion rate was higher in the non-smoker Asian females with pulmonary adenocarcinoma.
ALK mutations have been identified in approximately 2.4-13% of patients with NSCLC, occurring more frequently in adenocarcinomas and never and light smokers.