Department of Radiation Effects Research, National Institute of Radiological Sciences (NIRS), National Institutes for Quantum and Radiological Science and Technology (QST), Chiba, Japan.
Department of Radiological Sciences, Graduate School of Human Health Sciences, Tokyo Metropolitan University, Tokyo, Japan.
Anticancer Res. 2021 Jan;41(1):55-70. doi: 10.21873/anticanres.14751.
BACKGROUND/AIM: Our understanding of cancer risk from neutron exposure is limited. We aimed to reveal the characteristics of mammary carcinomas induced by neutrons.
Mammary carcinomas obtained from female Sprague-Dawley rats irradiated at 7 weeks of age with 0.97 Gy neutrons or 4 Gy γ-rays and from non-irradiated rats were classified into luminal and non-luminal subtypes by immunohistochemistry. Their mutational landscapes were determined by whole-exome sequencing.
Neutrons significantly raised the incidence of luminal mammary carcinomas over the non-luminal subtype. Somatic mutations were identified in cancer genes involved in several signalling pathways, including Keap1/Nrf2, Pi3k/Akt and Wnt/β-catenin. Focal copy-number losses involving cancer genes were observed mainly in carcinomas from the irradiated rats.
Neutrons increase the incidence of luminal mammary carcinomas, probably through gene mutations similar to those found in human breast cancers, and focal copy-number losses including cancer genes that are characteristics of radiation-induced mammary carcinomas.
背景/目的：我们对中子照射致癌风险的了解有限。本研究旨在揭示中子诱导的乳腺癌的特征。
7 周龄雌性 Sprague-Dawley 大鼠经 0.97 Gy 中子或 4 Gy γ 射线照射后，获得乳腺肿瘤，并通过免疫组织化学将其分为腔型和非腔型亚型。采用全外显子组测序确定其突变特征。
中子照射显著增加了腔型乳腺癌的发生率，而非腔型乳腺癌。在涉及多个信号通路的癌症基因中发现了体细胞突变，包括 Keap1/Nrf2、Pi3k/Akt 和 Wnt/β-catenin。在照射大鼠的肿瘤中主要观察到涉及癌症基因的局灶性拷贝数缺失。
中子照射增加了腔型乳腺癌的发生率，可能通过类似于人类乳腺癌的基因突变，以及局灶性拷贝数缺失，包括辐射诱导乳腺癌的特征性癌症基因。
