title: Assessment of the clinical relevance of 17q25.3 copy number and three-dimensional telomere organization in non-small lung cancer patients.
abstract: OBJECTIVE
  To identify potential biomarkers that may provide new therapeutic targets or prognostic indicators for non-small cell lung cancer (NSCLC), we investigated the three-dimensional (3D) organization of telomeres and cytoband 17q25.3 copy number in NSCLC tissues.
  
  
  METHODS
  NSCLC paraffin-embedded tissue specimens from 18 patients were assessed for 3D telomere organization by 3D nuclear telomere imaging followed by quantitative analysis. Patients were stratified by smoking, histology, and EGFR status. Cytoband 17q25.3 was examined by fluorescent in situ hybridization. Data from comparative genomic hybridization and/or single nucleotide polymorphism arrays for cytoband 17q25.3 were obtained and correlated with Q-FISH and 3D telomere results.
  
  
  RESULTS
  3D telomeric profiling demonstrated that the smokers, EGFR-negative, and squamous cell carcinoma subgroups tended to have higher numbers of lower-intensity telomeres, indicative of shorter telomeres, as well as higher numbers of telomeric aggregations compared to non-smokers, EGFR-positive, and adenocarcinomas, respectively. Gains of cytoband 17q25.3 in conjunction with an increase in the control region 17p11.2 were observed in 7 of 18 (38.9 %) patients, reflecting a gain of chromosome 17. Clonal gains of cytoband 17q25.3 were observed in 11 of 18 (61 %) patients, highlighting a potential biological significance for the genes in this region in NSCLC tumourigenesis.
  
  
  CONCLUSIONS
  The 3D telomere profiles may differentiate NSCLC patients with different histologies, EGFR, and smoking statuses, rendering them a potential biomarker for distinguishing these clinically relevant histological and molecular subtypes of lung cancer. Highly frequent clonal gain of cytoband 17q25.3 was also demonstrated, suggesting an important biological role for the genes in this region.
authors.affiliation: Genomic Centre for Cancer Research and Diagnosis, Manitoba Institute of Cell Biology, University of Manitoba, 675 McDermot Avenue, Room ON6045, Winnipeg, MB, Canada.|Division of Medical Oncology, Department of Medicine, Prince of Songkla University, Songkhla, Thailand.
authors.forename: Patrapim
authors.initials: P
authors.lastname: Sunpaweravong
authors.affiliation: Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Kelsie L
authors.initials: KL
authors.lastname: Thu
authors.affiliation: Pathology and Laboratory Medicine, University of British Columbia, Vancouver, BC, Canada.
authors.forename: Wan L
authors.initials: WL
authors.lastname: Lam
authors.affiliation: Genomic Centre for Cancer Research and Diagnosis, Manitoba Institute of Cell Biology, University of Manitoba, 675 McDermot Avenue, Room ON6045, Winnipeg, MB, Canada. Sabine.Mai@umanitoba.ca.
authors.forename: Sabine
authors.initials: S
authors.lastname: Mai
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D002886:Chromosomes, Human, Pair 17; D055028:Comparative Genomic Hybridization; D056915:DNA Copy Number Variations; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D020641:Polymorphism, Single Nucleotide; D012907:Smoking / Q000009:adverse effects*; D016019:Survival Analysis; D016615:Telomere / Q000235:genetics / Q000378:metabolism*
chemical_list: C512478:EGFR protein, human; D066246:ErbB Receptors
keywords: (non)Smoking; 3D telomere profiles; Chromosome 17q gain; EGFR; Non-small cell lung cancer