Association of BIM Deletion Polymorphism and BIM-γ RNA Expression in NSCLC with EGFR Mutation.
OBJECTIVE
This pilot study assessed the association of BIM deletion polymorphism and BIM RNA isoform in patients with EGFR-positive non-small cell lung cancer (NSCLC).


METHODS
The study included 33 patients with EGFR-positive NSCLC treated with gefitinib. BIM deletion polymorphism and BIM RNA isoform (EL/L/S/γ) were determined by polymerase chain reaction (PCR).


RESULTS
BIM-γ expression was significantly higher in patients with BIM deletion polymorphism than among those without BIM deletion polymorphism inside tumors (p=0.038) and around tumors (p=0.0024). Relative BIM-γ expression was significantly higher in patients with BIM deletion polymorphism than among those without BIM deletion polymorphism (p=0.0017). Patients with BIM-γ had significantly shorter progression-free survival than those without BIM-γ (median: 304 vs. 732 days; p=0.023).


CONCLUSIONS
Expression of BIM-γ mRNA and BIM deletion polymorphism were strongly associated. BIM-γ overexpression may have a role in apoptosis related to EGFR-tyrosine kinase inhibitor.
Division of Respiratory Medicine, Toho University School of Medicine, Tokyo, Japan kazutoshiisobe@med.toho-u.ac.jp.
Kazutoshi
K
Isobe
Division of Respiratory Medicine, Toho University School of Medicine, Tokyo, Japan.
Atsushi
A
Kakimoto
Division of Pathology, Toho University School of Medicine, Tokyo, Japan.
Tetsuo
T
Mikami
Division of Respiratory Medicine, Toho University School of Medicine, Tokyo, Japan.
Kyohei
K
Kaburaki
Division of Respiratory Medicine, Toho University School of Medicine, Tokyo, Japan.
Hiroshi
H
Kobayashi
Division of Respiratory Medicine, Toho University School of Medicine, Tokyo, Japan.
Takahiro
T
Yoshizawa
Division of Chest Surgery, Toho University School of Medicine, Tokyo, Japan.
Takashi
T
Makino
Division of Chest Surgery, Toho University School of Medicine, Tokyo, Japan.
Hajime
H
Otsuka
Division of Respiratory Medicine, Toho University School of Medicine, Tokyo, Japan.
G O
GO
Sano
Division of Respiratory Medicine, Toho University School of Medicine, Tokyo, Japan.
Keishi
K
Sugino
Division of Respiratory Medicine, Toho University School of Medicine, Tokyo, Japan.
Susumu
S
Sakamoto
Division of Respiratory Medicine, Toho University School of Medicine, Tokyo, Japan.
Yujiro
Y
Takai
Division of Surgical Pathology, Toho University School of Medicine, Tokyo, Japan.
Naobumi
N
Tochigi
Division of Pathology, Toho University School of Medicine, Tokyo, Japan.
Akira
A
Iyoda
Division of Respiratory Medicine, Toho University School of Medicine, Tokyo, Japan.
Sakae
S
Homma
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis / Q000187:drug effects; D000072224:Bcl-2-Like Protein 11 / Q000096:biosynthesis / Q000235:genetics*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D000077156:Gefitinib; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D047428:Protein Kinase Inhibitors / Q000008:administration & dosage; D011799:Quinazolines / Q000008:administration & dosage; D017384:Sequence Deletion
D000072224:Bcl-2-Like Protein 11; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; C512478:EGFR protein, human; D066246:ErbB Receptors; D000077156:Gefitinib
BIM; epidermal growth factor receptor tyrosine kinase inhibitor; non-small cell lung cancer