Mouse Lewis Lung Tumor Endothelial Cells

Whole-Exome Sequencing Reveals Distinct Mutational Landscape of Lewis Lung Carcinoma

Lewis lung carcinoma (LLC), as a widely used preclinical cancer model, has still not been genetically and genomically characterized. Here, He et al. performed a whole-exome sequencing analysis on the LLC cell line to elucidate its molecular characteristics and etiologies.

Whole-exome sequencing (WES) revealed that the LLC-derived C57BL mouse represents a previously unrecognized subline closely related to C57BL/6J, which they designated C57BL/6L ("L" for Lewis). Due to the absence of matched normal tissue, somatic mutations were identified by comparing LLC against the C57BL/6J reference genome, capturing variants acquired during tumorigenesis and those accumulated during laboratory passaging since 1951. The analysis identified 18,664 single nucleotide variants (SNVs) and 2,225 insertions/deletions (InDels). Coding regions harbored 5,082 SNVs, with nearly half causing non-synonymous changes (2,201 missense, 63 nonsense). Most InDels (95.6%) were in non-coding regions, while coding InDels predominantly resulted in frameshift or non-frameshift alterations. Mutation distribution was highly uneven, with prominent regional mutation clusters (≥6 consecutive substitutions within ≤10 kb) concentrated on chromosomes 2, 4, 6, 7, 8, 9, 11, and 13 (Fig. 1b), suggesting frequent structural rearrangements. Approximately 38% of all variants were homozygous, clustering primarily on chromosomes 4 and 11 (Fig. 1c). These clusters coincided with regional mutation clusters and likely arose through loss of heterozygosity (LOH) during genomic rearrangements. These findings define the unique mutational architecture of LLC and provide a critical genomic context for its use as a preclinical model.