KIF5B-RET Fusion gene may coincide oncogenic mutations of EGFR or KRAS gene in lung adenocarcinomas.
BACKGROUND
The KIF5B-RET rearrangement is detected with the frequency of 1 ~ 2% in 'triple marker'-negative lung adenocarcinomas, i.e., EGFR, KRAS and EML4-ALK wild type. These mutational changes are known to be mutually exclusive, but the co-existence of ALK rearrangement with activating mutations of EGFR is rarely found.


METHODS
We examined the KIF5B-RET fusion gene in frozen tissues from 154 surgically resected lung tumors using RT-PCR with direct sequencing and the mutation status of EGFR and KRAS genes using PNA clamping. We tested KIF5B-RET translocation in Formalin Fixed Paraffin Embedded using fluorescence in situ hybridization. We also measured RET mRNA and protein expression by RT-PCR and immunohistochemistry, respectively.


RESULTS
The existence of KIF5B-RET fusion gene was identified in 9 patients. The mean age was 67.2 and M: F ratio 4:5. Of 9 patients, 3 patients harbored wild type of EGFR and KRAS gene. However, KIF5B-RET fusion gene coincided with EGFR or KRAS mutation in 6 patients. These six pts were also positive for both RET break-apart probes (23.9%) and KIF5B-RET fusion (44.4%). However, there were no correlations between RET mRNA and protein expression in the KIF5B-RET-positive patients. The median disease free survival and overall survival were 23.9 months and 29.5 months, respectively.


CONCLUSIONS
Taken together, our data suggest one-step screening platform for KIF5B-RET as well as EGFR, K-RAS, ALK oncogenic mutations be necessary for lung adenocarcinoma patients because EGFR or KRAS mutation are not infrequently found in KIF5B-RET-positive patients.
Laboratory of Medical Oncology, Reaserch Institutes of Medical Science, The Catholic University of Korea, 222 Banpo-daero Seocho-gu, Seoul, 137-701, Republic of Korea.
Jeong-Oh
JO
Kim
Department of Medical Oncology, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-daero Seocho-gu, Seoul, Republic of Korea.
Jieun
J
Lee
Laboratory of Medical Oncology, Reaserch Institutes of Medical Science, The Catholic University of Korea, 222 Banpo-daero Seocho-gu, Seoul, 137-701, Republic of Korea.
Jung-Young
JY
Shin
Laboratory of Medical Oncology, Reaserch Institutes of Medical Science, The Catholic University of Korea, 222 Banpo-daero Seocho-gu, Seoul, 137-701, Republic of Korea.
Ji-Eun
JE
Oh
Division of Pathology, Seoul St.Mary's hospital, The Catholic University of Korea, 222 Banpo-daero Seocho-gu, Seoul, Republic of Korea.
Chan-Kwon
CK
Jung
Department of Thoracic and Cardiovascular Surgery, Seoul St.Mary's hospital, The Catholic University of Korea, 222 Banpo-daero Seocho-gu, Seoul, Republic of Korea.
Jae Kil
JK
Park
Department of Thoracic and Cardiovascular Surgery, Seoul St.Mary's hospital, The Catholic University of Korea, 222 Banpo-daero Seocho-gu, Seoul, Republic of Korea.
Sook-Whan
SW
Sung
Mirax Ltd, 334-1 Jangan-gu Suwon-si, Gyeonggi-do, Republic of Korea.
Sang-Ju
SJ
Bae
Mirax Ltd, 334-1 Jangan-gu Suwon-si, Gyeonggi-do, Republic of Korea.
Hyun-Jung
HJ
Min
Panagene Inc, 816 Tamnip-dong Yuseong-gu, Daejeon, Republic of Korea.
Dowon
D
Kim
Department of Internal Medicine, Kyungpook National University School of Medicine, 130 Dongdeok-ro Jung-gu, Daegu, Republic of Korea.
Jae Yong
JY
Park
Department of Medical Oncology, Seoul St. Mary's Hospital, The Catholic University of Korea, 222 Banpo-daero Seocho-gu, Seoul, Republic of Korea. jinkang@catholic.ac.kr.
Jin-Hyoung
JH
Kang
D000230:Adenocarcinoma / Q000235:genetics* / Q000401:mortality; D000077192:Adenocarcinoma of Lung; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis / Q000235:genetics; D004252:DNA Mutational Analysis; D018572:Disease-Free Survival; D005260:Female; D018773:Genes, erbB-1 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
D014408:Biomarkers, Tumor; C573239:KIF5B-RET fusion protein, human; C117307:KRAS protein, human; D015514:Oncogene Proteins, Fusion; D016283:Proto-Oncogene Proteins p21(ras)