Yang Dong, Zhang Weiyuan, Liang JunQing, Ma Kexin, Chen Peng, Lu Danni, Hao Wenjing
Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China.
Peking University People's Hospital, Beijing 100044, China.
Oncotarget. 2017 Dec 21;9(7):7332-7340. doi: 10.18632/oncotarget.23587. eCollection 2018 Jan 26.
Cervical cancer is the third most common cancer in women. Radiotherapy resistance remains a major obstacle for patients with cervical cancer. Somatic alterations in human genomes are responsible for radiotherapy resistance. Here, we performed single cell whole genome sequencing on 13 cells before radiotherapy and 12 cells after radiotherapy from a Chinese woman patient with cervical carcinoma. We identified one damaging mutation in NFKB1 (G430E), which showed significantly increased mutant allele frequency after radiotherapy than that before radiotherapy. Further functional assays showed that NFKB1 was a tumour suppressor in cervical cancer by inhibiting cell proliferation, colony formation and migration, while the mutation in NFKB1 could weaken the tumour suppressing functions of NFKB1. NFKB1 enhanced the sensitivity of cervical cancer cells to the effects of irradiation, and the mutation in NFKB1 weakened this effect. These results suggested that NFKB1 may be a potential molecular target in cervical cancer radiation therapy in the future.
宫颈癌是女性中第三大常见癌症。放疗抵抗仍然是宫颈癌患者面临的主要障碍。人类基因组中的体细胞改变是放疗抵抗的原因。在此，我们对一名中国宫颈癌女性患者放疗前的13个细胞和放疗后的12个细胞进行了单细胞全基因组测序。我们在NFKB1中鉴定出一个有害突变（G430E），该突变在放疗后的突变等位基因频率比放疗前显著增加。进一步的功能分析表明，NFKB1通过抑制细胞增殖、集落形成和迁移在宫颈癌中起肿瘤抑制作用，而NFKB1中的突变会削弱NFKB1的肿瘤抑制功能。NFKB1增强了宫颈癌细胞对辐射作用的敏感性，而NFKB1中的突变削弱了这种作用。这些结果表明，NFKB1未来可能是宫颈癌放射治疗中的一个潜在分子靶点。
