PMID- 26175310 OWN - NLM STAT- MEDLINE DCOM- 20160209 LR - 20191008 IS - 1097-0215 (Electronic) IS - 0020-7136 (Print) IS - 0020-7136 (Linking) VI - 138 IP - 1 DP - 2016 Jan 1 TI - 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. PG - 98-109 LID - 10.1002/ijc.29691 [doi] AB - 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. CI - Published 2015. This article is a U.S. Government work and is in the public domain in the USA. FAU - Wangsa, Darawalee AU - Wangsa D AD - Genetics Branch, Center For Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD. AD - Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. FAU - Chowdhury, Salim Akhter AU - Chowdhury SA AD - Joint Carnegie Mellon/University of Pittsburgh Ph.D. Program In Computational Biology, Carnegie Mellon University, Pittsburgh, PA. AD - Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA. FAU - Ryott, Michael AU - Ryott M AD - Department of Otorhinolaryngology, Sophiahemmet Hospital, Stockholm, Sweden. FAU - Gertz, E Michael AU - Gertz EM AD - Computational Biology Branch, National Center For Biotechnology Information, National Institutes of Health, Bethesda, MD. FAU - Elmberger, Goran AU - Elmberger G AD - Department of Laboratory Medicine, Pathology, Orebro University Hospital, Orebro, Sweden. FAU - Auer, Gert AU - Auer G AD - Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. FAU - Avall Lundqvist, Elisabeth AU - Avall Lundqvist E AD - Department of Oncology-Pathology, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden. AD - Department of Oncology And Department Of Clinical And Experimental Medicine, Linkoping University, Linkoping, Sweden. FAU - Kuffer, Stefan AU - Kuffer S AD - Institute of Pathology, University Medical Center Gottingen, Gottingen, Germany. FAU - Strobel, Philipp AU - Strobel P AD - Institute of Pathology, University Medical Center Gottingen, Gottingen, Germany. FAU - Schaffer, Alejandro A AU - Schaffer AA AD - Computational Biology Branch, National Center For Biotechnology Information, National Institutes of Health, Bethesda, MD. FAU - Schwartz, Russell AU - Schwartz R AD - Computational Biology Department, Carnegie Mellon University, Pittsburgh, PA. AD - Department of Biological Sciences, Carnegie Mellon University, Pittsburgh, PA. FAU - Munck-Wikland, Eva AU - Munck-Wikland E AD - Department of Oto-Rhino-Laryngology, Head And Neck Surgery, Karolinska University Hospital and Department of Clinical Science, Intervention and Technology, Karolinska Institutet, Stockholm, Sweden. FAU - Ried, Thomas AU - Ried T AD - Genetics Branch, Center For Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD. FAU - Heselmeyer-Haddad, Kerstin AU - Heselmeyer-Haddad K AD - Genetics Branch, Center For Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD. LA - eng GR - R01 AI076318/AI/NIAID NIH HHS/United States GR - 1R01AI076318/AI/NIAID NIH HHS/United States GR - R01 CA140214/CA/NCI NIH HHS/United States GR - Z01 LM000097-07/Intramural NIH HHS/United States GR - 1R01CA140214/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, N.I.H., Intramural PT - Research Support, Non-U.S. Gov't DEP - 20150828 PL - United States TA - Int J Cancer JT - International journal of cancer JID - 0042124 RN - 0 (Biomarkers, Tumor) SB - IM MH - Adult MH - Aged MH - Biomarkers, Tumor/*genetics MH - Carcinoma, Squamous Cell/*genetics/*mortality/pathology/virology MH - *DNA Copy Number Variations MH - Female MH - Human papillomavirus 16 MH - Humans MH - In Situ Hybridization, Fluorescence MH - Male MH - Middle Aged MH - Neoplasm Staging MH - Papillomavirus Infections MH - *Phylogeny MH - Prognosis MH - Risk Factors MH - Survival Analysis MH - Tongue Neoplasms/*genetics/*mortality/pathology/virology MH - Young Adult PMC - PMC4823771 MID - NIHMS773346 OTO - NOTNLM OT - FISH OT - HPV OT - genetic markers OT - oral tongue cancer OT - phylogenetic modeling EDAT- 2015/07/16 06:00 MHDA- 2016/02/10 06:00 PMCR- 2016/04/07 CRDT- 2015/07/16 06:00 PHST- 2014/10/30 00:00 [received] PHST- 2015/04/21 00:00 [revised] PHST- 2015/06/19 00:00 [accepted] PHST- 2015/07/16 06:00 [entrez] PHST- 2015/07/16 06:00 [pubmed] PHST- 2016/02/10 06:00 [medline] PHST- 2016/04/07 00:00 [pmc-release] AID - 10.1002/ijc.29691 [doi] PST - ppublish SO - Int J Cancer. 2016 Jan 1;138(1):98-109. doi: 10.1002/ijc.29691. Epub 2015 Aug 28.