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  3. Long-read Sequencing Reveals Repeat Expansions and Large Structural Variants in Oral Squamous Cell Carcinoma

Long-read Sequencing Reveals Repeat Expansions and Large Structural Variants in Oral Squamous Cell Carcinoma

  • Genomics Proteomics Bioinformatics. 2025 Dec 27:qzaf133. doi: 10.1093/gpbjnl/qzaf133.
Li Hu 1,  Jiaxun Zhang 1,  Zhuoyuan Zhang 2 3,  Ranlei Wei 1,  Jie Fu 2,  Xiaoxue Tang 2,  Xuyan Liu 1,  Lanfang Yuan 1,  Ziting Feng 1,  Sibo Wu 2,  Lin Xia 1,  Dan Xie 1
Affiliations

Affiliations

  • 1 Laboratory of Omics Technology and Bioinformatics, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
  • 2 Department of Head and Neck Cancer Surgery, West China School of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
  • 3 State Key Laboratory of Oral Diseases, West China School of Stomatology, Sichuan University, Chengdu, Sichuan 610041, China.
PMID: 41454621 DOI: 10.1093/gpbjnl/qzaf133
Abstract

Previous genomic studies have predominantly analyzed oral squamous cell carcinoma (OSCC) in conjunction with Other head and neck squamous cell carcinomas (HNSCC), constraining our comprehension of OSCC-specific structural variants (SVs). Here, we performed long-read whole-genome Sequencing on 16 paired OSCC tumor and blood samples to elucidate the biological functions of somatic SVs. We identified a total of 5775 high-confidence somatic SVs, including five recurrent simple repeat expansions (SREs). Notably, one SRE located within the promoter region of the OBI1 gene is present in 45% of OSCC samples. Knocking out this SRE in the HSC4 cell line significantly reduces the expression of OBI1, resulting in decreased proliferative and migratory capacities compared to wild-type cells. Furthermore, we found that the frequently amplified region 11q13 in HNSCC is prone to large-scale somatic SVs, affecting the expression of ANO1, FADD, and CTTN, thereby confirming the association of SVs in this region with OSCC development. Our study provides novel insights into the role of somatic SVs in OSCC, especially with respect to SREs and large-scale SVs in critical genomic regions, thereby enhancing our comprehension of the molecular pathogenesis of OSCC.

Keywords

Complex structural rearrangements; Nanopore sequencing; Oral squamous cell carcinoma; Simple repeat expansion; Somatic structural variants.

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