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  • Wangsa, DarawaleeNCI, MD 20892 USA; Karolinska University Hospital, Sweden (author)

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

  • Article/chapterEnglish2016

Publisher, publication year, extent ...

  • 2015-08-28
  • John Wiley & Sons,2016
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:liu-122643
  • https://urn.kb.se/resolve?urn=urn:nbn:se:liu:diva-122643URI
  • https://doi.org/10.1002/ijc.29691DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:132246530URI

Supplementary language notes

  • Language:English
  • Summary in:English

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  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • 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
  • 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.

Subject headings and genre

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  • Akhter Chowdhury, SalimCarnegie Mellon University, PA 15213 USA; Carnegie Mellon University, PA 15213 USA (author)
  • Ryott, MichaelSophiahemmet Hospital, Sweden (author)
  • Michael Gertz, E.NIH, MD 20892 USA (author)
  • Elmberger, GoranÖrebro University Hospital, Sweden (author)
  • Auer, GertKarolinska Institutet,Karolinska University Hospital, Sweden (author)
  • Åvall Lundqvist, ElisabethKarolinska Institutet,Linköpings universitet,Avdelningen för kliniska vetenskaper,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US,Karolinska University Hospital, Sweden(Swepub:liu)eliav51 (author)
  • Kueffer, StefanUniversity of Medical Centre Gottingen, Germany (author)
  • Stroebel, PhilippUniversity of Medical Centre Gottingen, Germany (author)
  • Schaeffer, Alejandro A.NIH, MD 20892 USA (author)
  • Schwartz, RussellCarnegie Mellon University, PA 15213 USA; Carnegie Mellon University, PA 15213 USA (author)
  • Munck-Wikland, EvaKarolinska Institutet,Karolinska University Hospital, Sweden; Karolinska Institute, Sweden (author)
  • Ried, ThomasNCI, MD 20892 USA (author)
  • Heselmeyer-Haddad, KerstinNCI, MD 20892 USA (author)
  • NCI, MD 20892 USA; Karolinska University Hospital, SwedenCarnegie Mellon University, PA 15213 USA; Carnegie Mellon University, PA 15213 USA (creator_code:org_t)

Related titles

  • In:International Journal of Cancer: John Wiley & Sons138:1, s. 98-1090020-71361097-0215

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