Title: Next-generation sequencing of disseminated tumor cells
Authors: Møller, Elen K *
Kumar, Parveen *
Voet, Thierry
Peterson, April
Van Loo, Peter
Mathiesen, Randi R
Fjelldal, Renathe
Grundstad, Jason
Borgen, Elin
Baumbusch, Lars O
Naume, Bjørn
Børresen-Dale, Anne-Lise
White, Kevin P
Nord, Silje
Kristensen, Vessela N # ×
Issue Date: 2013
Publisher: Frontiers Media S.A.
Series Title: Frontiers in Oncology vol:3 pages:320
Article number: 10.3389/fonc.2013.00320
Abstract: Disseminated tumor cells (DTCs) detected in the bone marrow have been shown as an independent prognostic factor for women with breast cancer. However, the mechanisms behind the tumor cell dissemination are still unclear and more detailed knowledge is needed to fully understand why some cells remain dormant and others metastasize. Sequencing of single cells has opened for the possibility to dissect the genetic content of subclones of a primary tumor, as well as DTCs. Previous studies of genetic changes in DTCs have employed single-cell array comparative genomic hybridization which provides information about larger aberrations. To date, next-generation sequencing provides the possibility to discover new, smaller, and copy neutral genetic changes. In this study, we performed whole-genome amplification and subsequently next-generation sequencing to analyze DTCs from two breast cancer patients. We compared copy-number profiles of the DTCs and the corresponding primary tumor generated from sequencing and SNP-comparative genomic hybridization (CGH) data, respectively. While one tumor revealed mostly whole-arm gains and losses, the other had more complex alterations, as well as subclonal amplification and deletions. Whole-arm gains or losses in the primary tumor were in general also observed in the corresponding DTC. Both primary tumors showed amplification of chromosome 1q and deletion of parts of chromosome 16q, which was recaptured in the corresponding DTCs. Interestingly, clear differences were also observed, indicating that the DTC underwent further evolution at the copy-number level. This study provides a proof-of-principle for sequencing of DTCs and correlation with primary copy-number profiles. The analyses allow insight into tumor cell dissemination and show ongoing copy-number evolution in DTCs compared to the primary tumors.
ISSN: 2234-943X
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Laboratory of Reproductive Genomics
Department of Human Genetics - miscellaneous
* (joint) first author
× corresponding author
# (joint) last author

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