Table 1.
Studies of somatic L1 activity in cancer genomes. Column three gives the total number of somatic L1 insertions discovered in the total number of tumors assayed; these estimates take validation rates into account when applicable.
| Reference | Tumor Type | Insertions (Tumors) | Important Findings |
|---|---|---|---|
| Miki et al. 1992 [52] | Colorectal | 1 (1) |
First genuine somatic L1 activity; L1 insertion in APC might have initiated colorectal cancer (CRC), but somewhat unclear |
| Iskow et al. 2010 [51] | Lung, brain | 8, 0 (20, 10) |
Introduced high-throughput L1-Seq assay; Established that somatic L1 activity occurs frequently in lung tumors, but not in brain tumors; Suggested that L1s might drive tumorigenesis; Found a hypomethylation signature that distinguishes L1-permissive lung tumors |
| Lee et al. 2012 [70] | Colorectal, prostate, ovarian, brain, blood | 178 (43) |
Somatic L1 activity only in epithelial tumors, absent from brain and blood; Genes with somatic L1 insertions typically had decreased expression; Compared features of somatic and germline L1s |
| Solyom et al. 2012 [71] | Colorectal | 72 (16) |
Positive correlation between patient age and number of somatic L1s; Most L1 insertions occurred after tumor initiation |
| Shukla et al. 2013 [72] | Liver | 12 (19) |
Intronic somatic L1 insertion into a regulatory element increased expression of candidate liver oncogene ST18; Suggested that L1s might be somatically active in normal liver cells |
| Pitkänen et al. 2014 [73] | Colorectal | 83 (92) |
All L1 insertions originated from one source element on Chromosome 22, in TTC28; These L1 insertions were previously mischaracterized as translocations |
| Helman et al. 2014 [74] | 11 types | 695 (976) |
Somatic L1 insertion in an exon of the PTEN tumor suppressor gene (TSG); Lung, colorectal, head and neck, and uterine cancers had highest L1 mobilization levels |
| Tubio et al. 2014 [75] | 12 types | 2711 (290) |
3 transductions make up 24% of somatic L1 activity; A small number of source elements gave rise to most L1 insertions with transductions; Active sources had promoter hypomethylation; Activity of sources fluctuates over the course of tumor evolution |
| Paterson et al. 2015 [76] | Esophageal | 5108 (43) |
The majority of L1s were discovered by searching for somatic poly(A) insertions, so some probably represent L1-mediated transposition of non-L1 sequence; Identified active source elements using 3 transductions |
| Rodić et al. 2015 [77] | Pancreatic | 409 (20) |
Inverse correlation between survival and both the number of somatic L1 insertions and ORF1p protein expression; Retrotransposition occurs throughout tumor development, but is discontinuous |
| Ewing et al. 2015 [78] | Colorectal, pancreatic, gastric, testicular | 104 (18) |
Frequent somatic L1 insertions in precancerous adenomas; Most somatic L1 insertions were clonal; Validated one somatic non-germline L1 insertion in normal colon; Suggested that L1 insertions are occurring in normal colon or very early in tumorigenesis |
| Doucet-O’Hare et al. 2015 [79] | Esophageal | 118 (20) |
Found somatic L1 insertions in patients with Barrett’s Esophagus (a cancer-predisposing condition) and esophageal cancer; L1 activity seen in patients that did not develop cancer; Suggested that somatic L1 activity could occur in normal or metaplastic cells |
| Scott et al. 2016 [80] | Colorectal | 27 (1) |
An L1-initiated CRC caused by L1 mutagenesis of APC TSG; Tumor initiated by activity of a hot, population-specific FL-L1 source element, which was hypomethylated and expressed in normal colon tissue; Demonstrated that L1s can evade somatic repression and initiate tumorigenesis |
| Achanta et al. 2016 [83] | Brain | 1 (10) |
Found one somatic L1 insertion in a secondary glioblastoma; Cannot rule out that this occurred in normal brain because compared to DNA from blood |
| Carreira et al. 2016 [84] | Brain | 0 (14) |
Could only validate one TPRT-independent somatic L1 insertion and one likely Alu-Alu recombination event; Conclude that L1 retrotransposition does not occur in primary glioblastoma or glioma |
| Tang et al. 2017 [81] | Ovarian; pancreatic | 35, 205 (8, 13) |
Found one somatic L1 insertion in BRCA1 TSG intron, in an ovarian cancer; Some pancreatic L1 insertions (76) were discovered in an earlier analysis of this same sequencing data [77] and used for methodological validation here |