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HPV 整合引起的中国人宫颈腺癌的基因组改变。

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

机构信息

Department of Obstetrics and Gynecology, Peking Union Medical College Hospital, Beijing, 100730, China.

Department of Obstetrics and Gynecology, China-Japan Friendship Hospital, Beijing, 100029, China.

出版信息

Cancer Gene Ther. 2021 Dec;28(12):1353-1364. doi: 10.1038/s41417-020-00283-4. Epub 2021 Jan 4.

DOI:10.1038/s41417-020-00283-4
PMID:33398034
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8636260/
Abstract

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.

摘要

人乳头瘤病毒（HPV）整合与子宫颈腺癌相关的基因组变化之间的关联尚未完全阐明。本研究旨在描述 20 例患者队列的基因组突变景观。HPV+和 HPV-组定义为患者在宿主基因组中是否存在 HPV 整合。通过全基因组测序（WGS）和全外显子组测序（WES）描述和比较这两组之间的遗传变化。WGS 鉴定出 2916 个拷贝数变异和 743 个结构变异。WES 鉴定出 6113 个体细胞突变，突变负担为 2.4 个突变/Mb。预测了 6 个基因作为驱动基因：PIK3CA、KRAS、TRAPPC12、NDN、GOLGA6L4 和 BAIAP3。PIK3CA、NDN、GOLGA6L4 和 BAIAP3 被认为是显著突变基因（SMGs）。95%（19/20）的宫颈癌患者检测到 HPV，其中 7 例（36.8%）有 HPV 整合（HPV+组）。总共在 HPV+组中确认了 1036 个具有体细胞突变的基因，而在没有 HPV 整合的组（HPV-组）中确认了 289 个具有体细胞突变的基因；两组之间只有 2.1%的基因共享。在 HPV+组中，GOLGA6L4 和 BAIAP3 被确认为 SMGs，而 PIK3CA、NDN、KRAS、FUT1 和 GOLGA6L64 在 HPV-组中被鉴定。HPV 整合后，ZDHHC3、PKD1P1 和 TGIF2 显示出拷贝数扩增。此外，HPV+组具有更多的新抗原。HPV 整合而不是 HPV 感染导致宫颈癌中不同的基因组变化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aef/8636260/990c9d067394/41417_2020_283_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aef/8636260/a0d3ec75e0b0/41417_2020_283_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aef/8636260/79e23dc6f811/41417_2020_283_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aef/8636260/8151f7dd7eb0/41417_2020_283_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aef/8636260/4daf322d4058/41417_2020_283_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aef/8636260/e6007cd8d194/41417_2020_283_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aef/8636260/fc93bed76fce/41417_2020_283_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aef/8636260/5c3678643e90/41417_2020_283_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aef/8636260/990c9d067394/41417_2020_283_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aef/8636260/a0d3ec75e0b0/41417_2020_283_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aef/8636260/79e23dc6f811/41417_2020_283_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aef/8636260/8151f7dd7eb0/41417_2020_283_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aef/8636260/4daf322d4058/41417_2020_283_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aef/8636260/e6007cd8d194/41417_2020_283_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aef/8636260/fc93bed76fce/41417_2020_283_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aef/8636260/5c3678643e90/41417_2020_283_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7aef/8636260/990c9d067394/41417_2020_283_Fig8_HTML.jpg

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