During tumor initiation and/or progression, encoded oncogenic proteins activated by translocations or mutations can alter cell proliferation and/or apoptosis

[3], resulting in MNK inhibitor transformation events. Fusion transcripts can be caused by chromosomal translocations and may occur more frequently in solid tumors than previously understood [2–4]. E2A-PBX1 fusion protein contains the transactivation domain of E2A and the DNA-binding domain of PBX1 and is generated by t(1;19)(q23;p13) translocation [5]. t(1;19) occurs in 5% of pre-B-cell acute lymphoid leukemias (ALL) in children and adults [6] and E2A-PBX1 has been widely Selleck BI 10773 characterized in ALL [5–15]. E2A-PBX1 can cause transformation in several cell types in vitro and induce lymphoblastic lymphomas in transgenic mice [7–9]. Target genes of E2A-PBX1 includes fibroblast growth factor (FGF)-15 [13], WNT-16 [14], and some novel genes [10], etc. Bmi-1 regulation of INK4A-ARF was required

for transformation of hematopoietic progenitors by E2A-PBX1 [15]. However, there has been no report on detection of E2A-PBX1 fusion transcripts in solid tumors. In this study, we investigated into the detection of E2A-PBX1 fusion transcripts in NSCLC and compared this genetic change with three other common mutations in NSCLC (i.e. k-ras, p53 and EGFR) [16–18]. These data suggest that E2A-PBX1 fusion transcripts caused by t(1;19)(q23;p13) may be a common somatic genetic change of importance in solid tumors and E2A-PBX1 may be a Selleckchem AG-881 novel target for prognosis and therapy in adenocarcinoma in situ (AIS) [19]. Methods Patients and tissue

specimens A total of 184 patients were chosen in this study. All eligible patients these without preoperative chemotherapy or radiation treatment underwent surgical resection of a primary NSCLC and had adequate mediastinal lymph node staging at UCSF between July 1997 and January 2007. Their clinical information of patients was summarized in Table  1. Information on clinical variables and patient follow-up were obtained from a prospectively maintained database including all subjects with banked tissue in the study. Patients consented to tissue specimen collection prospectively, and the study was approved by UCSF Human Research Protection Program Committee on Human Research. Tissue specimens were snap-frozen in liquid nitrogen at the time of the operation and stored in -150°C freezer. Table 1 Characteristics of NSCLC patients in the study cohort     Total (%) E2A-PBX1 positive (%) E2A-PBX1 negative (%) P value Median overall survival (95% CI) P value   Total 184 (100) 23 (12.5) 161 (87.5)   105.60 (55.41 ~ 155.79)   Age               Mean (years) 66.9 ± 12.0 66.0 ± 11.7 67.0 ± 12.1 0.698*       Range (years) 25-91 39-84 25-91         <71 109 (100) 13 (11.9) 96 (88.1) 0.777 69.00 (43.73 ~ 94.27) 0.7069   ≥71 75 (100) 10 (13.3) 65 (86.7)   105.60 (18.53 ~ 192.67)   Gender       0.215       Male 78 (100) 7 (9.0) 71 (91.0)   64.70 (NA) 0.