Bilous N I, Abramenko I V, Chumak A A, Dyagil I S, Martina Z V, Saenko V, Bazyka D A
State Institution «National Research Center for Radiation Medicine of the National Academy of Medical Sciences of Ukraine», 53 Melnykova str., Kyiv, 04050, Ukraine.
Department of Radiation Molecular Epidemiology, Atomic Bomb Disease Institute, Nagasaki University, Nagasaki, Japan.
Probl Radiac Med Radiobiol. 2018 Dec;23:283-301. doi: 10.33145/2304-8336-2018-23-283-301.
to analyze TP53, NOTCH1 and SF3B1 mutations in chronic lymphocytic leukemia (CLL) patients, sufferersof Chornobyl NPP accident to clarify the possible relationship between ionizing radiation (IR) and CLL.
Mutations of TP53, NOTCH1, and SF3B1 genes were studied by direct sequencing in the main group of 106 CLLpatients exposed to IR due to Chornobyl NPP accident and in the control group of 130 IR non-exposed CLL patients.
We found TP53 and SF3B1 mutations with similar incidence in both groups - 11.3 % and 10.0 % in the maingroup, and 12.7 % and 11.5 % in the control group, respectively. In contrast, the frequency of NOTCH1 mutationswas lower in IR-exposed patients (6.7 % vs 17.7 %; p = 0.012). TP53 mutations were seen with equal frequency amongmutated (11.1 %) and unmutated (11.8 %) immunoglobulin heavy-chain variable gene (IGHV) cases in IR-exposedCLL patients, while the tendency to prevalence of TP53 mutations in unmutated compared with mutated IGHV caseswas found in the control group (14.1 % and 5.6 %, correspondingly; p = 0.178). In IR-exposed group SF3B1 muta-tions were combined with mutations in TP53 almost in half of detected cases. In opposite, in the control group therewas mutual exclusivity between SF3B1 and TP53 lesions (p = 0.001). Among IR-exposed CLL patients we found two dif-ferent cases with identical rare mutation of TP53 gene - c.665C>T substitution (Pro222Leu). This substitution is verylikely to represent inherited TP53 mutation, which may influence CLL development under IR exposure.
Our preliminary data suggest that TP53 abnormalities are involved in CLL development in subjectsexposed at the Chornobyl accident and also a possible connection between inherited sensitivity to ionizing radia-tion caused by mutation in TP53, radiation and CLL development.
分析慢性淋巴细胞白血病（CLL）患者以及切尔诺贝利核电站事故受害者中TP53、NOTCH1和SF3B1基因的突变情况，以阐明电离辐射（IR）与CLL之间的可能关系。
通过直接测序研究了106名因切尔诺贝利核电站事故暴露于IR的CLL患者主要组以及130名未暴露于IR的CLL患者对照组中TP53、NOTCH1和SF3B1基因的突变情况。
我们发现两组中TP53和SF3B1突变的发生率相似——主要组分别为11.3%和10.0%，对照组分别为12.7%和11.5%。相反，暴露于IR的患者中NOTCH1突变的频率较低（6.7%对17.7%；p = 0.012）。在暴露于IR的CLL患者中，TP53突变在突变（11.1%）和未突变（11.8%）的免疫球蛋白重链可变基因（IGHV）病例中出现的频率相同，而在对照组中发现未突变的IGHV病例中TP53突变的流行趋势高于突变病例（分别为14.1%和5.6%；p = 0.178）。在暴露于IR的组中，几乎一半检测到的病例中SF3B1突变与TP53突变同时存在。相反，在对照组中，SF3B1和TP53病变之间存在相互排斥（p = 0.001）。在暴露于IR的CLL患者中，我们发现了两例具有相同TP53基因罕见突变——c.665C>T替换（Pro222Leu）的不同病例。这种替换很可能代表遗传性TP53突变，这可能会影响在IR暴露下CLL的发展。
我们的初步数据表明，TP53异常参与了切尔诺贝利事故暴露人群中CLL的发展，并且TP53突变引起的对电离辐射的遗传敏感性、辐射与CLL发展之间可能存在联系。
