Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
1p36 deletion is a marker for tumour dissemination in microsatellite stable stage II-III colon cancer
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Cancer Pharmacology and Computational Medicine.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Colorectal Surgery.
Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology, Molecular and Morphological Pathology.
Show others and affiliations
2014 (English)In: BMC Cancer, ISSN 1471-2407, E-ISSN 1471-2407, Vol. 14, 872- p.Article in journal (Refereed) Published
Abstract [en]

Background: The clinical behaviour of colon cancer is heterogeneous. Five-year overall survival is 50-65% with all stages included. Recurring somatic chromosomal alterations have been identified and some have shown potential as markers for dissemination of the tumour, which is responsible for most colon cancer deaths. We investigated 115 selected stage II-IV primary colon cancers for associations between chromosomal alterations and tumour dissemination. Methods: Follow-up was at least 5 years for stage II-III patients without distant recurrence. Affymetrix SNP 6.0 microarrays and allele-specific copy number analysis were used to identify chromosomal alterations. Fisher's exact test was used to associate alterations with tumour dissemination, detected at diagnosis (stage IV) or later as recurrent disease (stage II-III). Results: Loss of 1p36.11-21 was associated with tumour dissemination in microsatellite stable tumours of stage II-IV (odds ratio = 5.5). It was enriched to a similar extent in tumours with distant recurrence within stage II and stage III subgroups, and may therefore be used as a prognostic marker at diagnosis. Loss of 1p36.11-21 relative to average copy number of the genome showed similar prognostic value compared to absolute loss of copies. Therefore, the use of relative loss as a prognostic marker would benefit more patients by applying also to hyperploid cancer genomes. The association with tumour dissemination was supported by independent data from the The Cancer Genome Atlas. Conclusion: Deletions on 1p36 may be used to guide adjuvant treatment decisions in microsatellite stable colon cancer of stages II and III.

Place, publisher, year, edition, pages
2014. Vol. 14, 872- p.
Keyword [en]
Colon cancer, Prognostic marker, Allele-specific copy number analysis, Genome duplication, 1p36, Metastasis, Tumour dissemination
National Category
Cancer and Oncology
Identifiers
URN: urn:nbn:se:uu:diva-240088DOI: 10.1186/1471-2407-14-872ISI: 000345660000001PubMedID: 25420937OAI: oai:DiVA.org:uu-240088DiVA: diva2:775943
Available from: 2015-01-05 Created: 2015-01-05 Last updated: 2017-12-05Bibliographically approved
In thesis
1. Copy Number Analysis of Cancer
Open this publication in new window or tab >>Copy Number Analysis of Cancer
2015 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

By accurately describing cancer genomes, we may link genomic mutations to phenotypic effects and eventually treat cancer patients based on the molecular cause of their disease, rather than generalizing treatment based on cell morphology or tissue of origin.

Alteration of DNA copy number is a driving mutational process in the formation and progression of cancer. Deletions and amplifications of specific chromosomal regions are important for cancer diagnosis and prognosis, and copy number analysis has become standard practice for many clinicians and researchers. In this thesis we describe the development of two computational methods, TAPS and Patchwork, for analysis of genome-wide absolute allele-specific copy number per cell in tumour samples. TAPS is used with SNP microarray data and Patchwork with whole genome sequencing data. Both are suitable for unknown average ploidy of the tumour cells, are robust to admixture of genetically normal cells, and may be used to detect genetic heterogeneity in the tumour cell population. We also present two studies where TAPS was used to find copy number alterations associated with risk of recurrence after surgery, in ovarian cancer and colon cancer. We discuss the potential of such prognostic markers and the use of allele-specific copy number analysis in research and diagnostics.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2015. 42 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 1072
Keyword
chromosomes, oncology, bioinformatics
National Category
Bioinformatics (Computational Biology) Genetics Cancer and Oncology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Research subject
Bioinformatics; Oncology; Clinical Genetics
Identifiers
urn:nbn:se:uu:diva-244361 (URN)978-91-554-9175-8 (ISBN)
Public defence
2015-04-17, BMC E10:1307-1309, BMC, Husargatan 3, Uppsala, 13:00 (English)
Opponent
Supervisors
Available from: 2015-03-26 Created: 2015-02-16 Last updated: 2015-04-17

Open Access in DiVA

fulltext(2136 kB)343 downloads
File information
File name FULLTEXT01.pdfFile size 2136 kBChecksum SHA-512
e50a3c8850f2f6322bf5a35098daba523714b5efbd1ccb785fcee01f0849b783452fbd30976824e6ebf7d63e46bc545ee024aab8532e41a68f5459365e0935e5
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Mayrhofer, MarkusKultima, Hanna GöranssonBirgisson, HelgiSundström, MagnusMathot, LucyViklund, BjörnSjöblom, TobiasBotling, JohanMicke, PatrickPåhlman, LarsGlimelius, BengtIsaksson, Anders
By organisation
Science for Life Laboratory, SciLifeLabCancer Pharmacology and Computational MedicineColorectal SurgeryMolecular and Morphological PathologyGenomicsDepartment of Radiology, Oncology and Radiation ScienceOncology
In the same journal
BMC Cancer
Cancer and Oncology

Search outside of DiVA

GoogleGoogle Scholar
Total: 343 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 994 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf