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


CONCLUSIONS
Our study demonstrates that mutations in each part of the EGFR pathway were associated with different clinicopathologic features in patients with NSCLCs.
Lee
Shin Yup
SY
Department of Internal Medicine, School of Medicine, Kyungpook National University, Daegu, Republic of Korea.
Kim
Min Jung
MJ
Jin
Guang
G
Yoo
Seung Soo
SS
Park
Ji Young
JY
Choi
Jin Eun
JE
Jeon
Hyo Sung
HS
Cho
Sukki
S
Lee
Eung Bae
EB
Cha
Seung Ick
SI
Park
Tae-In
TI
Kim
Chang Ho
CH
Jung
Tae Hoon
TH
Park
Jae Yong
JY
D000091162:AMP-Activated Protein Kinase Kinases; D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000473:pathology; D058534:Class I Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D011905:Genes, ras / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D051059:PTEN Phosphohydrolase / Q000235:genetics; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011379:Prognosis; D017346:Protein Serine-Threonine Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D020893:Receptor, ErbB-3 / Q000235:genetics; D066247:Receptor, ErbB-4; D015398:Signal Transduction / Q000235:genetics*; D018631:ras Proteins / Q000235:genetics
D000091162:AMP-Activated Protein Kinase Kinases; D014408:Biomarkers, Tumor; D058534:Class I Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D051059:PTEN Phosphohydrolase; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D048493:Proto-Oncogene Proteins B-raf; D051057:Proto-Oncogene Proteins c-akt; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases; D020893:Receptor, ErbB-3; D066247:Receptor, ErbB-4; D018631:ras Proteins; C117307:KRAS protein, human; C484760:PIK3CA protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C587689:ERBB4 protein, human; C494918:AKT1 protein, human; C482119:BRAF protein, human; C109790:STK11 protein, human; C494929:PTEN protein, human