Open AccessIdentification of a Novel MAN1A1-ROS1 Fusion Gene Through mRNA-based Screening for Tyrosine Kinase Gene Aberrations in a Patient with Leiomyosarcoma
Author(s) -
Yoshiyuki Suehara,
Shinji Kohsaka,
Takuo Hayashi,
Keisuke Akaike,
Aiko Kurisaki-Arakawa,
Shingo Sato,
Eisuke Kobayashi,
Sho Mizuno,
Toshihide Ueno,
Takeshi Morii,
Tomotake Okuma,
Taisei Kurihara,
Naoto Hasegawa,
Kei Sano,
Keita Sasa,
Taketo Okubo,
Youngji Kim,
Hiroyuki Mano,
Tsuyoshi Saito
Publication year - 2020
Publication title -
clinical orthopaedics and related research
Language(s) - English
Resource type - Journals
eISSN - 1528-1132
pISSN - 0009-921X
DOI - 10.1097/corr.0000000000001548
Subject(s) - tyrosine kinase , receptor tyrosine kinase , cancer research , fusion gene , medicine , leiomyosarcoma , sarcoma , tyrosine kinase inhibitor , pathology , biology , gene , cancer , receptor , genetics
Soft tissue sarcomas are a heterogeneous group of rare malignant tumors. Advanced soft tissue sarcomas have a poor prognosis, and effective systemic therapies have not been established. Tyrosine kinases are increasingly being used as therapeutic targets for a variety of cancers and soft tissue sarcomas. Although complex karyotype sarcomas typically tend to carry more potentially actionable genetic alterations than do translocation-associated sarcomas (fusion gene sarcomas), based on our database review, we found that leiomyosarcoma and malignant peripheral nerve sheath tumors have lower frequencies of potential targets than other nontranslocation soft tissue sarcomas. We theorized that both leiomyosarcoma and malignant peripheral nerve sheath tumors might be included in any unique translocations. Furthermore, if tyrosine kinase imbalances, especially fusion genes, occur in patients with leiomyosarcomas and malignant peripheral nerve sheath tumors, tyrosine kinase inhibitors might be a drug development target for this sarcoma. In this study, we used a tyrosine kinase screening system that could detect an imbalance in mRNA between 5'- and 3'-sides in tyrosine kinase genes to identify potential novel therapeutic tyrosine kinase targets for soft tissue sarcomas.