Evidence for L1-associated DNA rearrangements and negligible L1 retrotransposition in glioblastoma multiforme
Carreira, Patricia E ; Ewing, Adam D ; Li, Guibo ; Schauer, Stephanie N ; Upton, Kyle R ; Fagg, Allister C ; Morell, Santiago ; Kindlova, Michaela ; Gerdes, Patricia LU
and Richardson, Sandra R
, et al.
(2016)
In Mobile DNA
7.
p.1-14
- Abstract
BACKGROUND: LINE-1 (L1) retrotransposons are a notable endogenous source of mutagenesis in mammals. Notably, cancer cells can support unusual L1 retrotransposition and L1-associated sequence rearrangement mechanisms following DNA damage. Recent reports suggest that L1 is mobile in epithelial tumours and neural cells but, paradoxically, not in brain cancers.
RESULTS: Here, using retrotransposon capture sequencing (RC-seq), we surveyed L1 mutations in 14 tumours classified as glioblastoma multiforme (GBM) or as a lower grade glioma. In four GBM tumours, we characterised one probable endonuclease-independent L1 insertion, two L1-associated rearrangements and one likely Alu-Alu recombination event adjacent to an L1. These mutations... (More)
BACKGROUND: LINE-1 (L1) retrotransposons are a notable endogenous source of mutagenesis in mammals. Notably, cancer cells can support unusual L1 retrotransposition and L1-associated sequence rearrangement mechanisms following DNA damage. Recent reports suggest that L1 is mobile in epithelial tumours and neural cells but, paradoxically, not in brain cancers.
RESULTS: Here, using retrotransposon capture sequencing (RC-seq), we surveyed L1 mutations in 14 tumours classified as glioblastoma multiforme (GBM) or as a lower grade glioma. In four GBM tumours, we characterised one probable endonuclease-independent L1 insertion, two L1-associated rearrangements and one likely Alu-Alu recombination event adjacent to an L1. These mutations included PCR validated intronic events in MeCP2 and EGFR. Despite sequencing L1 integration sites at up to 250× depth by RC-seq, we found no tumour-specific, endonuclease-dependent L1 insertions. Whole genome sequencing analysis of the tumours carrying the MeCP2 and EGFR L1 mutations also revealed no endonuclease-dependent L1 insertions. In a complementary in vitro assay, wild-type and endonuclease mutant L1 reporter constructs each mobilised very inefficiently in four cultured GBM cell lines.
CONCLUSIONS: These experiments altogether highlight the consistent absence of canonical L1 retrotransposition in GBM tumours and cultured cell lines, as well as atypical L1-associated sequence rearrangements following DNA damage in vivo.
(Less)
- author
- Carreira, Patricia E
; Ewing, Adam D
; Li, Guibo
; Schauer, Stephanie N
; Upton, Kyle R
; Fagg, Allister C
; Morell, Santiago
; Kindlova, Michaela
; Gerdes, Patricia
LU
and Richardson, Sandra R
, et al. (More)
- Carreira, Patricia E
; Ewing, Adam D
; Li, Guibo
; Schauer, Stephanie N
; Upton, Kyle R
; Fagg, Allister C
; Morell, Santiago
; Kindlova, Michaela
; Gerdes, Patricia
LU
; Richardson, Sandra R
; Li, Bo
LU
; Gerhardt, Daniel J
; Wang, Jun
; Brennan, Paul M
and Faulkner, Geoffrey J
(Less)
- publishing date
- 2016
- type
- Contribution to journal
- publication status
- published
- in
- Mobile DNA
- volume
- 7
- article number
- 21
- pages
- 1 - 14
- publisher
- BioMed Central (BMC)
- external identifiers
-
- pmid:27843499
- scopus:84999622498
- ISSN
- 1759-8753
- DOI
- 10.1186/s13100-016-0076-6
- language
- English
- LU publication?
- no
- id
- b008e045-a7e5-41c2-81d3-64b87d399cfc
- date added to LUP
- 2024-06-10 16:15:40
- date last changed
- 2024-06-12 03:06:28
@article{b008e045-a7e5-41c2-81d3-64b87d399cfc,
abstract = {{<p>BACKGROUND: LINE-1 (L1) retrotransposons are a notable endogenous source of mutagenesis in mammals. Notably, cancer cells can support unusual L1 retrotransposition and L1-associated sequence rearrangement mechanisms following DNA damage. Recent reports suggest that L1 is mobile in epithelial tumours and neural cells but, paradoxically, not in brain cancers.</p><p>RESULTS: Here, using retrotransposon capture sequencing (RC-seq), we surveyed L1 mutations in 14 tumours classified as glioblastoma multiforme (GBM) or as a lower grade glioma. In four GBM tumours, we characterised one probable endonuclease-independent L1 insertion, two L1-associated rearrangements and one likely Alu-Alu recombination event adjacent to an L1. These mutations included PCR validated intronic events in MeCP2 and EGFR. Despite sequencing L1 integration sites at up to 250× depth by RC-seq, we found no tumour-specific, endonuclease-dependent L1 insertions. Whole genome sequencing analysis of the tumours carrying the MeCP2 and EGFR L1 mutations also revealed no endonuclease-dependent L1 insertions. In a complementary in vitro assay, wild-type and endonuclease mutant L1 reporter constructs each mobilised very inefficiently in four cultured GBM cell lines.</p><p>CONCLUSIONS: These experiments altogether highlight the consistent absence of canonical L1 retrotransposition in GBM tumours and cultured cell lines, as well as atypical L1-associated sequence rearrangements following DNA damage in vivo.</p>}},
author = {{Carreira, Patricia E and Ewing, Adam D and Li, Guibo and Schauer, Stephanie N and Upton, Kyle R and Fagg, Allister C and Morell, Santiago and Kindlova, Michaela and Gerdes, Patricia and Richardson, Sandra R and Li, Bo and Gerhardt, Daniel J and Wang, Jun and Brennan, Paul M and Faulkner, Geoffrey J}},
issn = {{1759-8753}},
language = {{eng}},
pages = {{1--14}},
publisher = {{BioMed Central (BMC)}},
series = {{Mobile DNA}},
title = {{Evidence for L1-associated DNA rearrangements and negligible L1 retrotransposition in glioblastoma multiforme}},
url = {{http://dx.doi.org/10.1186/s13100-016-0076-6}},
doi = {{10.1186/s13100-016-0076-6}},
volume = {{7}},
year = {{2016}},
}