Open AccessDetection of novel paraja ring finger 2‐fer tyrosine kinase mRNA chimeras is associated with poor postoperative prognosis in non‐small cell lung cancer
Author(s) -
Kawakami Masanori,
Ishikawa Rie,
Amano Yosuke,
Sunohara Mitsuhiro,
Watanabe Kousuke,
Ohishi Nobuya,
Yatomi Yutaka,
Nakajima Jun,
Fukayama Masashi,
Nagase Takahide,
Takai Daiya
Publication year - 2013
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.12250
Subject(s) - tyrosine kinase , medicine , messenger rna , lung cancer , cancer research , biology , receptor , gene , biochemistry
Previously, we reported that the overexpression of fer tyrosine kinase ( FER ), a non‐receptor tyrosine kinase, is correlated with poor postoperative prognosis and cancer‐cell survival in non‐small cell lung cancer ( NSCLC ). In the present study, we further analyzed FER ‐overexpressed NSCLC cases and identified various patterns of chimeric mRNA s, composed of paraja ring finger 2 ( PJA 2) and FER . We detected no genomic rearrangements between PJA 2 and FER and attributed these chimeric mRNA s to alterations at the transcriptome level: i.e., trans ‐splicing. Several chimeric patterns were detected concurrently in each patient, and the pattern sets varied among patients, although the pattern in which PJA 2 exon 1 was fused to FER exon 3 (designated as P e1‐ F e3 mRNA ) was detected constantly. Therefore, in a wide screening for PJA 2‐ FER mRNA s in NSCLC , we focused on this chimeric pattern as a representative chimera. In analyses of 167 NSCLC samples, P e1‐ F e3 mRNA was identified in about 10% of the patients, and the presence of chimeric mRNA was significantly correlated with a high expression level of parental FER mRNA . Furthermore, we found that the detection of P e1‐ F e3 mRNA was correlated with poor postoperative survival periods in NSCLC , consistent with a previous finding in which FER overexpression was correlated with poor postoperative prognosis in NSCLC . This report is the first to suggest a correlation between chimeric mRNA and the expression level of parental mRNA . Furthermore, our findings may be clinically beneficial, suggesting that PJA 2‐ FER mRNA s might serve as a novel prognostic biomarker in NSCLC .