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Gynecol Oncol. 2017 Dec;147(3):642-647. doi: 10.1016/j.ygyno.2017.09.032. Epub 2017 Oct 9.

LINE-1 retrotransposon-mediated DNA transductions in endometriosis associated ovarian cancers.

Author information

1
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
2
Department of Molecular Oncology, BC Cancer Agency, Vancouver, BC, Canada.
3
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada; Department of Gynecology and Obstetrics, University of British Columbia, Vancouver, BC, Canada.
4
Department of Human Genetics, McGill University, Research Institute of the McGill University Health Centre, Montreal, QC, Canada.
5
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada; Department of Molecular Oncology, BC Cancer Agency, Vancouver, BC, Canada.
6
Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada; Department of Molecular Oncology, BC Cancer Agency, Vancouver, BC, Canada. Electronic address: dhuntsma@bccancer.bc.ca.

Abstract

OBJECTIVE:

Endometrioid (ENOC) and clear cell ovarian carcinoma (CCOC) share a common precursor lesion, endometriosis, hence the designation endometriosis associated ovarian cancers (EAOC). Long interspersed nuclear element 1 (LINE-1 or L1), is a family of mobile genetic elements activated in many cancers capable of moving neighboring DNA through 3' transductions. Here we investigated the involvement of specific L1-mediated transductions in EAOCs.

METHODS:

Through whole genome sequencing, we identified active L1-mediated transductions originating within the TTC28 gene in 34% (10/29) of ENOC and 31% (11/35) of CCOC cases. We used PCR and capillary sequencing to assess the presence of specific TTC28-L1 transductions in formalin-fixed paraffin-embedded (FFPE) blocks from six different anatomical sites (five tumors and one normal control) for four ENOC and three CCOC cases, and compared the results to the presence of single nucleotide variations (SNVs)/frame shift (fs) mutations detected using multiplex PCR and next generation sequencing.

RESULTS:

TTC28-L1 mediated transductions were identified in at least three tumor samplings in all cases, and were present in all five tumor samplings in 5/7 (71%) cases. In these cases, KRAS, PIK3CA, CTNNB1, ARID1A, and PTEN mutations were found across all tumor sites while other selected SNV/fs mutations of unknown significance were present at varying allelic frequencies.

CONCLUSION:

The TTC28-L1 transductions along with classical driver mutations were near ubiquitous across the tumors, suggesting that L1 activation likely occurred early in the development of EAOCs. TTC28-L1 transductions could potentially be used to determine clonal relationships and to track ovarian cancer progression.

KEYWORDS:

Clear cell ovarian cancer; Endometrioid ovarian cancer; Endometriosis associated ovarian cancers; LINE-1 retrotransposon; LINE1-mediated DNA transduction; TTC28-L1

PMID:
29032825
DOI:
10.1016/j.ygyno.2017.09.032
[Indexed for MEDLINE]

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