Single cell whole genome sequencing reveals that NFKB1 mutation affects radiotherapy sensitivity in cervical cancer
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Dong Yang1, Weiyuan Zhang1, JunQing Liang2, Kexin Ma1, Peng Chen1, Danni Lu1 and Wenjing Hao1
1Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China
2Peking University People’s Hospital, Beijing 100044, China
Weiyuan Zhang, email: [email protected]
Keywords: cervical cancer; radiotherapy; single cell sequencing; somatic mutation; gene
Abbreviations: NFKB1: nuclear factor-kappa beta 1; PIK3CA: phosphoinositide-3-kinase, catalytic, alpha polypeptide; TP53: Tumor protein p53
Received: July 27, 2017 Accepted: December 04, 2017 Published: December 21, 2017
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.
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