liu.seSearch for publications in DiVA
Change search
ReferencesLink to record
Permanent link

Direct link
Phylogenetic analysis of multiple FISH markers in oral tongue squamous cell carcinoma suggests that a diverse distribution of copy number changes is associated with poor prognosis
NCI, MD 20892 USA; Karolinska University Hospital, Sweden.
Carnegie Mellon University, PA 15213 USA; Carnegie Mellon University, PA 15213 USA.
Sophiahemmet Hospital, Sweden.
NIH, MD 20892 USA.
Show others and affiliations
2016 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 138, no 1, 98-109 p.Article in journal (Refereed) Published
Abstract [en]

Oral tongue squamous cell carcinoma (OTSCC) is associated with poor prognosis. To improve prognostication, we analyzed four gene probes (TERC, CCND1, EGFR and TP53) and the centromere probe CEP4 as a marker of chromosomal instability, using fluorescence in situ hybridization (FISH) in single cells from the tumors of sixty-five OTSCC patients (Stage I, n=15; Stage II, n=30; Stage III, n=7; Stage IV, n=13). Unsupervised hierarchical clustering of the FISH data distinguished three clusters related to smoking status. Copy number increases of all five markers were found to be correlated to non-smoking habits, while smokers in this cohort had low-level copy number gains. Using the phylogenetic modeling software FISHtrees, we constructed models of tumor progression for each patient based on the four gene probes. Then, we derived test statistics on the models that are significant predictors of disease-free and overall survival, independent of tumor stage and smoking status in multivariate analysis. The patients whose tumors were modeled as progressing by a more diverse distribution of copy number changes across the four genes have poorer prognosis. This is consistent with the view that multiple genetic pathways need to become deregulated in order for cancer to progress. Whats new? Oral tongue squamous cell carcinoma (OTSCC) is a rare head and neck cancer that typically is asymptomatic in early stages. Hence, in order to improve prognosis in OTSCC, predictive biomarkers that are independent of tumor stage must be identified. Here, using four fluorescence in situ hybridization (FISH) gene probes and the software FISHtrees, phylogenetic tree models of tumor progression in OTSCC patients were constructed. Analyses of the models showed that the more diverse the changes within the four marker genes, the worse the outcome in OTSCC. The markers predicted survival independent of smoking behavior and tumor stage.

Place, publisher, year, edition, pages
WILEY-BLACKWELL , 2016. Vol. 138, no 1, 98-109 p.
Keyword [en]
oral tongue cancer; FISH; genetic markers; phylogenetic modeling; HPV
National Category
Clinical Medicine
URN: urn:nbn:se:liu:diva-122643DOI: 10.1002/ijc.29691ISI: 000363203600014PubMedID: 26175310OAI: diva2:871770

Funding Agencies|National Institutes of Health (NIH), National Cancer Institute, National Library of Medicine (Intramural Research Program) NIH Extramural grants [1R01CA140214, 1R01AI076318]; Swedish Cancer Society (Cancerfonden); Cancer Society of Stockholm (Cancerforeningen); Laryngfonden; Karolinska Institutet

Available from: 2015-11-16 Created: 2015-11-13 Last updated: 2015-11-16

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Åvall Lundqvist, Elisabeth
By organisation
Division of Clinical SciencesFaculty of Medicine and Health Sciences
In the same journal
International Journal of Cancer
Clinical Medicine

Search outside of DiVA

GoogleGoogle Scholar
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

Altmetric score

Total: 129 hits
ReferencesLink to record
Permanent link

Direct link