El Yacoubi Hind, Lemine Sow Mohamed, El Ghouti Meryem, Kettani Fouad, Gamra Lamia, Mestari Amina, Jabri Lamia, Elghissassi Ibrahim, Errihani Hassan
Faculty of Medicine and Pharmacy, Mohammed V University, Rabat, Morocco.
Department of Medical Oncology, National Institute of Oncology, Rabat, Morocco.
Gulf J Oncolog. 2020 May;1(33):40-44.
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.
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.
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).
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.
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.
表皮生长因子受体（EGFR）突变是一组异质性的基因改变，主要在肺腺癌（AC）中被发现。它们发生在EGFR基因的第18至20外显子。常见的EGFR突变是第19外显子缺失和第21外显子替换，而第18和第20外显子的突变则较为罕见。它们对酪氨酸激酶抑制剂（TKI）的反应不同，常见的EGFR突变对TKI更敏感，反应率和生存率更高，而罕见的EGFR突变则对TKI耐药，预后和临床结果较差。本研究的目的是报告一组携带EGFR阳性突变的摩洛哥肺腺癌患者中罕见EGFR突变的频率和特征。
从334例EGFR检测申请中收集所有携带EGFR突变的摩洛哥肺腺癌患者病例。常见的EGFR突变定义为第19外显子缺失和第21外显子替换，而第18和第20外显子的突变则被视为罕见EGFR突变。报告患者特征，并在常见和罕见EGFR突变两组之间进行比较。
在所有申请检测的334例中，73例EGFR突变呈阳性。常见的EGFR突变占89%（65/73）。8例（11%）存在罕见EGFR突变。罕见EGFR突变中，第18外显子突变占62.5%（5/8），第20外显子突变占37.5%（3/8）。表达罕见EGFR突变的肿瘤患者中经常吸烟者的频率显著高于具有常见EGFR突变的肿瘤患者（p=0.013）。
本研究中发现的频率与文献数据一致。然而，我们发现罕见EGFR突变大多发生在第18外显子而非第20外显子，这一发现与现有文献不一致。因此，我们可以认为携带罕见EGFR突变的摩洛哥患者可能从TKI治疗中获益更多。
罕见EGFR突变是肺腺癌中基因改变的一个异质性亚组。对它们的研究值得真正关注。摩洛哥患者中约十分之一的肺腺癌肿瘤携带罕见EGFR突变。需要进一步进行更大规模患者的前瞻性研究，以评估其具体特征和结果。
