ABSTRACT
BACKGROUND: Epidermal growth factor receptor (EGFR) mutations are a heterogeneous group of genetic alterations mainly identified in lung adenocarcinoma (AC). They occur in exon 18 to 20 of the EGFR gene. Common EGFR mutations are deletions in exon 19 and substitutions in exon 21, while mutations in exon 18 and exon 20 are rare. Their response to tyrosine kinase inhibitors (TKI) is different, common EGFR mutations are more sensitive to TKI with better response rate and survival, whereas rare EGFR mutations are TKI resistant with poor prognosis and clinical outcomes. The objective of the present study was to report the frequency and characteristics of rare EGFR mutations in a group of Moroccan patients with lung AC harboring a positive EGFR mutation. PATIENTS AND METHODS: All cases of Moroccan patients with lung AC harboring mutated EGFR were collected from 334 EGFR test requested. Common EGFR mutations were defined as deletions in exon 19 and substitutions in exon 21 while mutation in exons 18 and 20 were qualified as rare EGFR mutations. Patients' characteristics were reported and compared between the two groups of common and rare EGFR mutations. RESULTS: EGFR mutations were positive in 73/334 of all requested tests. Common EGFR mutations accounted 89% (65/73). Rare EGFR mutations were present in 8 cases (11%). Rare EGFR mutations were composed of 62.5% exon 18 mutations (5/8) and 37.5% exon 20 mutation (3/8). The frequency of regular smokers in patients with tumors expressing rare EGFR mutations was significantly higher than that found in patients with tumors having common EGFR mutations (p=0.013). DISCUSSION: The frequency found in the present study was consistent with the literature data. However, we found that rare EGFR mutations occurred mostly in exon 18 rather than exon 20, findings that are discordant with the available literature. Thus, we could suggest that Moroccan patients with rare EGFR mutations would benefit more from TKI treatment. CONCLUSION: Rare EGFR mutations are a heterogeneous subset of genetic alterations in lung AC. Their study deserves a real relevant interest. Some one tenth of lung AC tumors in Moroccan patients harbor a rare EGFR mutation. Further prospective studies are needed, in larger numbers of patients, to assess their specific characteristics and outcomes.