Abstract: It has been found that BRG1 and BRM have a synthetic-lethal relationship, and that a treatment for inhibiting BRM is a promising approach for treating a BRG1-deficient cancer having no mutation in known therapeutic target genes. Moreover, it has also been revealed that, in this therapeutic strategy, a BRM inhibitor may be administered to a cancer patient after the selection based on BRG1 function suppression, thus enabling an efficient treatment based on the companion diagnosis.

Abstract: 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.

Abstract: [PROBLEMS] To identify mutations that can serve as indicators for predicting the effectiveness of drug treatments in cancers such as lung cancer; to provide a means for detecting said mutations; and to provide a means for identifying, based on said mutations, patients with cancer or subjects with a risk of cancer, in which drugs targeting genes having said mutations or proteins encoded by said genes show a therapeutic effect. [MEANS FOR SOLVING] A method for detecting a gene fusion serving as a responsible mutation (driver mutation) for cancer, the method comprising the step of detecting any one of an EZR-ERBB4 fusion polynucleotide, a KIAA1468-RET fusion polynucleotide, a TRIM24-a BRAF fusion polynucleotide, a CD74-NRG1 fusion polynucleotide, and an SLC3A2-NRG1 fusion polynucleotide, or a polypeptide encoded thereby, in an isolated sample from a subject with cancer.

Abstract: 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.