title: Frequent L1 retrotranspositions originating from TTC28 in colorectal cancer.
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.
authors.affiliation: Genome-Scale Biology Research Program, Research Programs Unit, University of Helsinki, Helsinki, Finland.
authors.forename: Esa
authors.initials: E
authors.lastname: Pitkänen
authors.forename: Tatiana
authors.initials: T
authors.lastname: Cajuso
authors.forename: Riku
authors.initials: R
authors.lastname: Katainen
authors.forename: Eevi
authors.initials: E
authors.lastname: Kaasinen
authors.forename: Niko
authors.initials: N
authors.lastname: Välimäki
authors.forename: Kimmo
authors.initials: K
authors.lastname: Palin
authors.forename: Jussi
authors.initials: J
authors.lastname: Taipale
authors.forename: Lauri A
authors.initials: LA
authors.lastname: Aaltonen
authors.forename: Outi
authors.initials: O
authors.lastname: Kilpivaara
mesh_terms: D002471:Cell Transformation, Neoplastic / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D023281:Genomics; D006801:Humans; D020084:Long Interspersed Nucleotide Elements; D018626:Retroelements / Q000235:genetics*
chemical_list: D018626:Retroelements