Single cell whole genome sequencing reveals that NFKB1 mutation affects radiotherapy sensitivity in cervical cancer

摘要

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.