Abstract
BackgroundTumorigenesis is a multi-step process which is accompanied by substantial changes in genome organization. The development of these changes is not only a random process, but rather comprise specific DNA regions that are prone to the reorganization process.ResultsWe have analyzed previously published SNP arrays from three different cancer types (pancreatic adenocarcinoma, breast cancer and metastatic melanoma) and from non-malignant control samples. We calculated segmental copy number variations as well as breakpoint regions. Some of these regions were not randomly involved in genome reorganization since we detected fifteen of them in at least 20% of all tumor samples and one region on chromosome 9 where 43% of tumors have a breakpoint. Further, the top-15 breakpoint regions show an association to known fragile sites. The relevance of these common breakpoint regions was further confirmed by analyzing SNP arrays from 917 cancer cell lines.ConclusionOur analyses suggest that genome reorganization is common in tumorigenesis and that some breakpoint regions can be found across all cancer types, while others exclusively occur in specific entities.
Highlights
Tumorigenesis is a multi-step process which is accompanied by substantial changes in genome organization
Tumorigenesis is a stepwise process, which involves multiple genetic, epigenetic and genomic events to transform a normal cell into a tumor cell [1,2,3,4,5,6].Genomic changes like copy number variations (CNVs) or segmental copy number variations increase throughout tumorigenesis [7,8,9] and are caused by various mechanisms, like fork stalling during replication or nonallelic homologous recombination [10,11,12]
single-nucleotide polymorphism (SNP) CNVs in different tumor entities To study the changes in genome reorganization during tumorigenesis, we analyzed previously published SNP arrays from 111 cancer samples: 25 pancreatic ductal adenocarcinoma, 22 pancreatic adenocarcinomas (PDAC) derived cell lines, 16 metastatic melanoma and 48 breast cancer samples
Summary
Tumorigenesis is a multi-step process which is accompanied by substantial changes in genome organization The development of these changes is a random process, but rather comprise specific DNA regions that are prone to the reorganization process. Tumorigenesis is a stepwise process, which involves multiple genetic, epigenetic and genomic events to transform a normal cell into a tumor cell [1,2,3,4,5,6].Genomic changes like copy number variations (CNVs) or segmental copy number variations (segCNVs) increase throughout tumorigenesis [7,8,9] and are caused by various mechanisms, like fork stalling during replication or nonallelic homologous recombination [10,11,12] These changes can affect the chromatin structure and the spatial localization of specific genes, the DNA sequence like single nucleotide mutations, amplifications, deletions or translocations as well as changes of karyotypes like aneuploidies [1, 13,14,15,16]. CFS instability is an early step in tumorigenesis and could be responsible for genome reorganization in cancer [23, 25,26,27,28,29]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
