Genomic alterations caused by HPV integration in a cohort of Chinese endocervical adenocarcinomas

• Published in: Cancer gene therapy Vol. 28; no. 12; pp. 1353 - 1364
• Main Authors: Li, Wenhui, Lei, Wanjun, Chao, Xiaopei, Song, Xiaochen, Bi, Yalan, Wu, Huanwen, Wu, Ming, Li, Lei
• Format: Journal Article
• Language: English
• Published: New York Nature Publishing Group US 01.12.2021; Nature Publishing Group
• Subjects: 45/23; 45/43; 692/699/67/1517/1371; 692/699/67/68; Adenocarcinoma; Adenocarcinoma - genetics; Adenocarcinoma - pathology; Biomedical and Life Sciences; Biomedicine; Cancer; Care and treatment; Cervical cancer; Cervix; China; Cohort Studies; Complications and side effects; Copy number; Diagnosis; Female; Gene Expression; Gene mutations; Gene Therapy; Genomes; Genomics; Genomics - methods; Health aspects; High-Throughput Nucleotide Sequencing - methods; Human papillomavirus; Humans; Integration; Mutation; Neoantigens; Observations; Papillomaviridae - genetics; Papillomavirus infections; Patient outcomes; Risk factors; Uterine Cervical Neoplasms - genetics; Uterine Cervical Neoplasms - pathology; Uterus; Whole genome sequencing; China
• ISSN: 0929-1903; 1476-5500
• DOI: 10.1038/s41417-020-00283-4

The association between human papillomavirus (HPV) integration and relevant genomic changes in uterine cervical adenocarcinoma is poorly understood. This study is to depict the genomic mutational landscape in a cohort of 20 patients. HPV+ and HPV− groups were defined as patients with and without HPV integration in the host genome. The genetic changes between these two groups were described and compared by whole-genome sequencing (WGS) and whole-exome sequencing (WES). WGS identified 2916 copy number variations and 743 structural variations. WES identified 6113 somatic mutations, with a mutational burden of 2.4 mutations/Mb. Six genes were predicted as driver genes: PIK3CA, KRAS, TRAPPC12, NDN, GOLGA6L4 and BAIAP3. PIK3CA, NDN, GOLGA6L4, and BAIAP3 were recognized as significantly mutated genes (SMGs). HPV was detected in 95% (19/20) of patients with cervical adenocarcinoma, 7 of whom (36.8%) had HPV integration (HPV+ group). In total, 1036 genes with somatic mutations were confirmed in the HPV+ group, while 289 genes with somatic mutations were confirmed in the group without HPV integration (HPV− group); only 2.1% were shared between the two groups. In the HPV+ group, GOLGA6L4 and BAIAP3 were confirmed as SMGs, while PIK3CA, NDN, KRAS, FUT1, and GOLGA6L64 were identified in the HPV− group. ZDHHC3, PKD1P1, and TGIF2 showed copy number amplifications after HPV integration. In addition, the HPV+ group had significantly more neoantigens. HPV integration rather than HPV infection results in different genomic changes in cervical adenocarcinoma.