Purpose: The acquisition of recurrent/metastatic potential by a tumor cell defines a critical step of malignant progression. However, the understanding of metastatic progression at the molecular level is scarce for cervical carcinomas (CES).

Materials and Methods: In this study, we performed comprehensive genomic, transcriptomic and viral profiling of five pairs of primary (CES-P) and matched recurrent/metastatic tumors (CES-R/M) with high risk human papillomavirus.

Results: Whole exome sequencing revealed mutation features of CES-R/M such as elevated mutation burdens and prevalent copy number alterations compared to their matched CES-P. A relative deficit of APOBEC-related mutation signatures accompanying the transcriptional down-regulation of APOBEC3A was also observed for CES-R/M. Mutations on genes encoding epigenetic regulators were also commonly observed as CES-R/M-specific alterations. Immunoprofiling and gene set analysis further revealed that CES-P were enriched with transcripts representing activated anticancer immunity such as cytolytic scores and interferon-gamma pathway but CES-R/M showed the up-regulation of genes involved in epithelial-mesenchymal transition and angiogenesis. Viral capture sequencing also revealed the hotspots of viral integration such as 12q13. Moreover, we found that the transcriptional upregulation of POSTN and downregulation of APOBEC3A were associated with unfavorable clinical outcomes in CES.

Conclusions: The comprehensive genomic and transcriptomic profiling of a rare cohort including CES-R/M identified metastases-specific features to advance the molecular understanding into the CES metastatic progression with potential clinical implication.

Citation Format: Youn Jin Choi, Yu Yeon Jung. Integrative analysis of recurrent-metastatic progression in high-risk human papillomavirus cervical carcinomas [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr LB-209.