Somatic repetitive element insertions Define New Biomarkers in Pan-cancer genome

Xia Lin; Kailing Tu; Huan Wang; Xuyan Liu; Yahui Liu; Qi‐Lin Zhang; Ziting Feng; Chunyan Yu; Maolin Li; Yan Huang; Jing Wang; Ranlei Wei; Tianfu Zeng; Xuenan Pi; Chen Ling; Qianwen Zhang; Yixin Qiao; Shengzhong Hou; Zhuoyuan Zhang; Ailin Wei; Haotian Liao; Wenhao Guo; Jifeng Liu; Zhong Wu; Zhoufeng Wang; Ang Li; Weiming Li; Dan Xie

doi:10.1101/2025.02.19.638966

GenomicsbioRxivFeb 19, 2025

Preprint

Somatic repetitive element insertions Define New Biomarkers in Pan-cancer genome

Xia Lin iD, Kailing Tu iD, Huan Wang iD, Xuyan Liu iD, Yahui Liu iD, Qi‐Lin Zhang iD, Ziting Feng iD, Chunyan Yu iD, Maolin Li iD, Yan Huang iD, Jing Wang iD, Ranlei Wei iD, Tianfu Zeng iD, Xuenan Pi iD, Chen Ling, Qianwen Zhang iD, Yixin Qiao iD, Shengzhong Hou, Zhuoyuan Zhang iD, Ailin Wei iD, Haotian Liao iD, Wenhao Guo iD, Jifeng Liu iD, Zhong Wu iD, Zhoufeng Wang iD, , Dan Xie iD

Abstract

Repetitive elements insertions (REIs), including tandem repeat insertions (TRIs) and transposable element insertions (TEIs), constitute >90% of large-scale (>50bp) somatic insertions and are linked to diseases and cancer biomarkers. However, the genomic landscape of large-scale REIs in pan-cancer has not been well-characterized due to short-read sequencing limitations. Here, we detected somatic REIs in 325 cancer genomes across 12 cancer types using long-read whole-genome sequencing and customized algorithms. The diverse sequence patterns of somatic TRIs and the insertion mechanisms of somatic TEIs were characterized across different cancer types. We identified 152 high-frequency somatic TRIs, with 10 showing pan-cancer characteristics, including TRIs in SHROOM2, PALMD, and the enhancer of PTPRZ1. The MHC class II gene cluster exhibited the highest somatic TEI abundance, affecting [~]40% tumors. Adenocarcinomas and squamous cell carcinomas exhibited differing TEI distributions within this region. Our study highlights REIs as important but under-explored markers for personalized cancer diagnosis and immunotherapy.

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