Locus-specific LINE-1 expression in clinical ovarian cancer specimens at the single-cell level. Locus-specific LINE-1 expression in clinical ovarian cancer specimens at the single-cell level

Long interspersed nuclear elements (LINE-1s or L1s) are a group of retrotransposons that can copy themselves within a genome. In our species, it is the most successful transposon in nucleotide content. L1 expression is generally mild in normal human tissues, but the activity has been shown to increase significantly in many cancers. Only few studies have examined L1 expression at single-cell resolution, thus it is undetermined whether L1 reactivation occurs solely in malignant cells within tumors. One of the cancer types with frequent L1 activity is high-grade serous ovarian carcinoma (HGSOC). Here, we identified locus-specific L1 expression with 3’ single-cell RNA sequencing in pre- and post-chemotherapy HGSOC sample pairs from 11 patients, and in fallopian tube samples from five healthy women. Although L1 expression quantification with the chosen technique was challenging due to the repetitive nature of L1 elements, we found evidence of genuine L1 expression. The expression levels were similar in pre- and post-chemotherapy samples, indicating that L1 transcriptional activity was unaffected by the treatment. Furthermore, we found that L1 activity was negatively associated with the expression of MYC target genes, a finding that supports earlier literature of MYC being an L1 suppressor. Overall design: We studied LINE-1 expression in 22 high-grade serous ovarian cancer patient samples collected concurrently with both laparoscopy and interval debulking surgery from 11 women, as well as in five non-cancerous fallopian tube or fimbria tissue samples from five healthy post-menopausal women. We used scRNA-seq to get a single-cell level view of the expression profiles. ---------------------------- Authors state: Raw data files are not included. The raw data has been uploaded to EGA (EGAS00001006246 for fallopian tube/fibmriae samples, EGAS00001005010 for cancer samples) in order to comply with data protection regulations.