Identification of new ALK and RET gene fusions from colorectal and lung cancer biopsies.
Applying a next-generation sequencing assay targeting 145 cancer-relevant genes in 40 colorectal cancer and 24 non-small cell lung cancer formalin-fixed paraffin-embedded tissue specimens identified at least one clinically relevant genomic alteration in 59% of the samples and revealed two gene fusions, C2orf44-ALK in a colorectal cancer sample and KIF5B-RET in a lung adenocarcinoma. Further screening of 561 lung adenocarcinomas identified 11 additional tumors with KIF5B-RET gene fusions (2.0%; 95% CI 0.8-3.1%). Cells expressing oncogenic KIF5B-RET are sensitive to multi-kinase inhibitors that inhibit RET.
Foundation Medicine, Cambridge, Massachusetts, USA.
Doron
D
Lipson
Marzia
M
Capelletti
Roman
R
Yelensky
Geoff
G
Otto
Alex
A
Parker
Mirna
M
Jarosz
John A
JA
Curran
Sohail
S
Balasubramanian
Troy
T
Bloom
Kristina W
KW
Brennan
Amy
A
Donahue
Sean R
SR
Downing
Garrett M
GM
Frampton
Lazaro
L
Garcia
Frank
F
Juhn
Kathy C
KC
Mitchell
Emily
E
White
Jared
J
White
Zac
Z
Zwirko
Tamar
T
Peretz
Hovav
H
Nechushtan
Lior
L
Soussan-Gutman
Jhingook
J
Kim
Hidefumi
H
Sasaki
Hyeong Ryul
HR
Kim
Seung-il
SI
Park
Dalia
D
Ercan
Christine E
CE
Sheehan
Jeffrey S
JS
Ross
Maureen T
MT
Cronin
Pasi A
PA
Jänne
Philip J
PJ
Stephens
D000077548:Anaplastic Lymphoma Kinase; D000818:Animals; D001706:Biopsy; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D002471:Cell Transformation, Neoplastic / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D016547:Kinesins / Q000037:antagonists & inhibitors / Q000235:genetics*; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D051379:Mice; D041681:NIH 3T3 Cells; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D051096:Proto-Oncogene Proteins c-ret / Q000037:antagonists & inhibitors / Q000235:genetics*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*
C488101:KIF5B protein, human; D015514:Oncogene Proteins, Fusion; D047428:Protein Kinase Inhibitors; C000626173:ALK protein, human; C000626174:Alk protein, mouse; D000077548:Anaplastic Lymphoma Kinase; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; D020794:Receptor Protein-Tyrosine Kinases; D016547:Kinesins