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Published on: July 27, 2019
Frequent L1 retrotranspositions originating from TTC28 in colorectal cancer
Esa Pitkänen1, Tatiana Cajuso, Riku Katainen
1Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland.
Abstract:
L1 element retrotranspositions have been found to alter expression of genes neighboring the insertion sites, potentially involving them in tumorigenesis and tumor progression. In colorectal cancer (CRC), L1 insertions have been found to target genes with a role in tumorigenesis. Structural changes such as L1 insertions are identifiable by whole genome sequencing (WGS). In this study, we observed frequent somatic L1 retrotranspositions originating from TTC28 using deep coverage WGS data from 92 CRC tumor-normal sample pairs. In two cases the event had targeted NOVA1 gene (p=0.025). In addition, a germline retrotransposition event from TTC28 to GABRA4 was found to be a common polymorphism in the Finnish population. Thus while some events may be tumorigenic, others are likely to be neutral. Our data contradict a recent study where a similar signal in TTC28 was interpreted as a common inactivating translocation. While much work remains to be performed to understand the biological significance of retrotranspositions in cancer, accurate identification of these events is a prerequisite for success.
Insights
Frequent L1 retrotranspositions from TTC28 were found in colorectal cancer (CRC) tumors. Some L1 insertions targeted genes like NOVA1, while others were common neutral polymorphisms, highlighting the need for accurate event identification.
Area of Science:
- Genomics
- Cancer Biology
- Molecular Genetics
Background:
- L1 element retrotranspositions can alter gene expression and contribute to cancer.
- Colorectal cancer (CRC) is a significant health concern where genetic alterations play a key role.
- Accurate identification of structural variations like L1 insertions is crucial for understanding cancer development.
Purpose of the Study:
- To investigate the frequency and origin of somatic L1 retrotranspositions in colorectal cancer.
- To identify specific genes targeted by L1 insertions in CRC.
- To differentiate between potentially tumorigenic and neutral retrotransposition events.
Main Methods:
- Whole genome sequencing (WGS) of 92 colorectal cancer tumor-normal sample pairs.
- Deep coverage sequencing data analysis to detect somatic L1 retrotranspositions.
- Bioinformatic analysis to identify insertion sites and affected genes.
Main Results:
- Frequent somatic L1 retrotranspositions originating from the TTC28 gene were observed in CRC.
- The NOVA1 gene was targeted by L1 insertions in two CRC cases (p=0.025).
- A common germline retrotransposition from TTC28 to GABRA4 was identified as a polymorphism in the Finnish population.
Conclusions:
- Somatic L1 retrotranspositions from TTC28 occur frequently in colorectal cancer.
- While some L1 events may be tumorigenic, others, like the TTC28-GABRA4 event, are likely neutral polymorphisms.
- Accurate identification of L1 retrotranspositions is essential for understanding their biological significance in cancer.
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