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. 2010 Nov;5(11):1734-40.
doi: 10.1097/JTO.0b013e3181f0beca.

Somatic mutations in epidermal growth factor receptor signaling pathway genes in non-small cell lung cancers

Shin Yup Lee  1 , Min Jung Kim, Guang Jin, Seung Soo Yoo, Ji Young Park, Jin Eun Choi, Hyo Sung Jeon, Sukki Cho, Eung Bae Lee, Seung Ick Cha, Tae-In Park, Chang Ho Kim, Tae Hoon Jung, Jae Yong Park
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Free article

Somatic mutations in epidermal growth factor receptor signaling pathway genes in non-small cell lung cancers

Shin Yup Lee et al. J Thorac Oncol. 2010 Nov.
Free article

Erratum in

  • J Thorac Oncol. 2011 Jun;6(6):1147

Abstract

Introduction: Epidermal growth factor receptor (EGFR) signaling pathway plays a crucial role in the development and progression of lung cancer. We searched for mutations of EGFR pathway genes in non-small cell lung cancers (NSCLCs) and analyzed their relationship with clinicopathologic features.

Methods: Mutations of EGFR, ERBB2, ERBB3, ERBB4, KRAS, NRAS, BRAF, PTEN, PIK3CA, LKB1, and AKT1 genes were determined by direct sequencing in 173 surgically resected NSCLCs--56 squamous cell carcinomas (SCCs) and 117 adenocarcinomas (ACs).

Results: Of the 173 NSCLCs, a total of 65 mutations were detected in 63 (36.4%) tumors--10 (17.9%) in SCCs and 53 (45.3%) in ACs. Mutations in EGFR pathway genes were significantly more frequent in women and ACs than in women and SCCs (p = 0.02 and p < 0.001, respectively). The mutations occurred in a mutually exclusive pattern. When the genes were divided into three subgroups according to their roles in the signaling cascade, mutations in the EGFR/ERBB2 and KRAS/BRAF genes were more frequent in ACs than in SCCs (p < 0.001 and p = 0.01, respectively). In marked contrast, mutations in the PIK3CA/PTEN were more frequent in SCCs than in ACs (p = 0.002). Furthermore, mutations in the PIK3CA/PTEN genes were more frequent in smokers (p = 0.04).

Discussion: Our study demonstrates that mutations in each part of the EGFR pathway were associated with different clinicopathologic features in patients with NSCLCs.

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