Detection of EML4-ALK fusion genes in non-small cell lung cancer patients with clinical features associated with EGFR mutations.
EML4-ALK fusion genes have been recognized as novel "driver mutations" in a small subset of non-small cell lung cancers (NSCLC). The frequency of EML4-ALK fusions in NSCLC patients who have clinical characteristics related to EGFR mutation remains unknown. We screened 102 Chinese patients with NSCLC based on one or more of the following characteristics: female, no or light smoking history, and adenocarcinoma histology. EML4-ALK fusion genes were identified by RT-PCR, whereas EGFR (Exons 18-21) and KRAS (Exons 1 and 2) mutations were detected by DNA sequencing. Eight specimens (8%) were positive for EML4-ALK fusions, with seven being Variant 1 and one Variant 2. There were 44 (43%) and 17 (16%) patients harboring EGFR and KRAS mutations, respectively. Thirty-one (31%) cases were wild type for EML4-ALK, EGFR, and KRAS mutations. Of the eight patients with EML4-ALK, none had an EGFR mutation, whereas a KRAS mutation was detected in one patient. Histologically, five of the EML4-ALK positive tumors were adenocarcinoma and two were mixed adenosquamous carcinoma; only one was a squamous carcinoma. Our data support the conclusion that the EML4-ALK fusion gene defines a new molecular subset of NSCLC with distinct pathologic features.
No. 2 Department of Chemotherapy, Affiliated Tumor Hospital, Guangxi Medical University, Guangxi, China.
Zhou
Z
Shaozhang
Lin
L
Xiaomei
Zeng
Z
Aiping
He
H
Jianbo
Song
S
Xiangqun
Yu
Y
Qitao
D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D018196:Carcinoma, Adenosquamous / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D066246:ErbB Receptors / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology; D008175:Lung Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D018631:ras Proteins / Q000235:genetics*
C522504:EML4-ALK fusion protein, human; C117307:KRAS protein, human; D015514:Oncogene Proteins, Fusion; D011518:Proto-Oncogene Proteins; C512478:EGFR protein, human; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins