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

作者：Dong Yang, Weiyuan Zhang, Junqing Liang, Kexin Ma, Peng Chen, Danni Lu, Wenjing Hao · 发表于：Oncotarget · 年份：2017 · DOI：10.18632/oncotarget.23587 · 被引用次数：24 · 研究领域：Cancer-related molecular mechanisms research、Mycobacterium research and diagnosis、Cytokine Signaling Pathways and Interactions

// Dong Yang 1 , Weiyuan Zhang 1 , JunQing Liang 2 , Kexin Ma 1 , Peng Chen 1 , Danni Lu 1 and Wenjing Hao 1 1 Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing 100026, China 2 Peking University People’s Hospital, Beijing 100044, China Correspondence to: Weiyuan Zhang, email: zhangwy9921@hotmail.com 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 ABSTRACT 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 functi...