@article{oai:repo.qst.go.jp:00086025,
 author = {Hirotaka, Tachibana and Kazuhiro, Daino and Atsuko, Ishikawa and Takamitsu, Morioka and Yi, Shang and Mari, Ogawa and Akira, Matsuura and Yoshiya, Shimada and Shizuko, Kakinuma and Hirotaka, Tachibana and Kazuhiro, Daino and Atsuko, Ishikawa and Takamitsu, Morioka and Yi, Shang and Mari, Ogawa and Yoshiya, Shimada and Shizuko, Kakinuma},
 journal = {Carcinogenesis},
 month = {Apr},
 note = {Epidemiological studies have revealed a radiation-related increase in the risk of developing acute lymphoblastic leukemia (ALL). Our recent study revealed early induction and increased risk of precursor B-cell (pB) lymphomas in mice after radiation exposure. However, the genomic landscape of radiation-induced B-cell lymphomas remains unclear. To identify the relevant genetic alterations in mice, whole-exome sequencing was performed on both early-onset and late-onset B-cell lymphomas that developed spontaneously or after gamma-irradiation. In addition to multiple driver mutations, the data revealed that interstitial deletion of chromosome 4, including Pax5, and missense mutations in Jak3 are unique genomic alterations in radiation-induced, early-onset B-cell lymphomas. RNA sequencing revealed a pB-cell-type gene-expression profile with no involvement of known fusion genes for human ALLs in the early-onset B-cell lymphomas. Activation of Jak3/Stat5 signaling in early-onset B-cell lymphomas was validated using western capillary electrophoresis. Those features were similar to those of Philadelphia chromosome–like ALL. Our data suggest a critical role for Pax5 loss-of-function mutations in initiating B-cell leukemogenesis coupled with activation of Jak3/Stat5 signaling as a basis for the rapid development of radiation-induced pB-ALL. These molecular signatures for radiation-induced cancers will inform both risk assessment and potential targeted therapies for pB-ALL.},
 title = {Genomic profile of radiation-induced early-onset mouse B-cell lymphoma recapitulates features of Philadelphia chromosome–like acute lymphoblastic leukemia in humans},
 year = {2022}
}