Method for determining effectiveness of cancer treatment by assessing the presence of a KIF5B-RET chimeric gene
In order to identify a gene that can serve as an indicator for predicting the effectiveness of a drug treatment of cancer and to provide a novel method for predicting the effectiveness of a drug treatment targeting said gene, lung adenocarcinomas were subjected to whole-transcriptome sequencing. As a result, in-frame fusion transcripts between the KIF5B gene and the RET gene were identified. The KIF5B-RET gene fusions were detected in 6 out of 319 (2%) LADC specimens from Japanese individuals and 1 out of 80 (1%) LADC specimens from U.S.A. individuals. None of the seven subjects revealed known activating mutations such as EGFR, KRAS or ALK oncogenes; thus, said gene fusions were found to be responsible mutations (driver mutations) for oncogenesis. Since said gene fusions are considered to induce constitutive activation of RET tyrosine kinase protein, it was found that treatments with RET tyrosine kinase inhibitors are effective in patients with detection of said gene fusions.
1. A method for determining the effectiveness of a cancer treatment with a RET tyrosine kinase inhibitor, the method comprising the step of detecting the presence or absence of a polynucleotide in a sample isolated from a patient, wherein the polynucleotide is selected from a group consisting of the DNA sequences of SEQ ID NOs: 5, 7, 9 or 11 and encodes a polypeptide comprising a N-terminal moiety of a KIF5B protein and a C-terminal moiety of a RET protein fused together, the N-terminal moiety of the KIF5B protein comprising a motor domain located on the N-terminal side of the KIF5B and part of all coiled-coil domain of KIF5B protein, the C-terminal moiety of the RET protein comprising a kinase domain located on the C-terminal side of the RET protein, wherein in a case where the presence of the polynucleotide is detected, the cancer treatment with the RET tyrosine kinase inhibitor is determined to be highly effective in the patient.