Long Interspersed Element-1 Protein Expression Is a Hallmark of Many Human Cancers

Abstract

Cancers comprise a heterogeneous group of human diseases. Unifying characteristics include unchecked abilities of tumor cells to proliferate and spread anatomically, and the presence of clonal advantageous genetic changes. However, universal and highly specific tumor markers are unknown. Herein, we report widespread long interspersed element-1 (LINE-1) repeat expression in human cancers. We show that nearly half of all human cancers are immunoreactive for a LINE-1-encoded protein. LINE-1 protein expression is a common feature of many types of high-grade malignant cancers, is rarely detected in early stages of tumorigenesis, and is absent from normal somatic tissues. Studies have shown that LINE-1 contributes to genetic changes in cancers, with somatic LINE-1 insertions seen in selected types of human cancers, particularly colon cancer. We sought to correlate this observation with expression of the LINE-1-encoded protein, open reading frame 1 protein, and found that LINE-1 open reading frame 1 protein is a surprisingly broad, yet highly tumor-specific, antigen.

Human transposon insertion profiling: Analysis, visualization and identification of somatic LINE-1 insertions in ovarian cancer

“…These cases are representative of one of the most lethal malignant diseases in women, and we have previously reported high levels of LINE-1-encoded protein expression in these malignancies (37). Using TIPseq and TIPseqHunter, we found a total of 36 somatically acquired, tumor-specific insertions in five of the eight individuals.…”

“…High proportions of both types of tumors aberrantly express LINE-1 encoded ORF1p protein (37), an RNA-binding protein critical for LINE-1 retrotransposition. Both have previously been shown to permit somatic retrotransposition events (22,25,27).…”

LINE-1 in cancer: multifaceted functions and potential clinical implications

“…miRNAs and lncRNAs may regulate gene expression directly or indirectly through competing endogenous RNA (ceRNA) networks. 68 In normal somatic cells, L1 retrotransposition is suppressed 22,31 and L1 transcripts are degraded or processed into regulatory RNAs that maintain cell homeostasis, 19,21,24,66,67 whereas in cancer, one study found that L1 transcripts were potentially biased toward cDNA formation and retrotransposition, 69 leading to speculation that deregulated regulatory RNA networks may drive tumorigenesis.…”

“…22,25 However, in line with L1 hypomethylation during tumorigenesis, [31][32][33][34] L1s can be reactivated and may participate in the pathological processes of cancer initiation and progression. 3,9,35 In 1988, Morse et al 36 reported a case of L1 insertion into c-myc gene in a breast cancer sample.…”

“…31 They may participate in tumorigenesis and their expression profiles can be of potential clinical significance. A study of breast cancer by Chen et al, 74 for example, revealed that the majority of invasive cancers expressed L1 proteins in the cytoplasm, with 28-31% of them showing nuclear expression.…”