title: Intratumoral genomic heterogeneity in advanced head and neck cancer detected by comparative genomic hybridization.
abstract: OBJECTIVE
  Little is known about the extent of intratumoral genetic heterogeneity in head and neck squamous cell carcinoma (HNSCC).
  
  
  METHODS
  Therefore, we examined 79 stage III and IV primary HNSCCs and matched lymph node metastases for over- and underrepresentation of specific chromosome regions by comparative genomic hybridization.
  
  
  RESULTS
  The overall ratio of gains and losses was higher in metastases (M) than in primary (P) tumors (4/1 vs. 2.5/1). Gains of 3q (78.1% P vs. 87.5% M) and 11q (78.1% P vs. 62.5% M), and deletions of 3p (43.8% P vs. 34.4% M) and 9p (31.3% P vs. 15.6% M) were most frequently detected. The highest rate of intratumoral discordance was observed for primary tumors and corresponding metastases (32.8%) compared to matched pairs of 2 metastases (26.5%), and of 2 anatomically distinct sides of 1 primary tumor (24.3%). Furthermore, the discordance rate was dependent on the primary tumor site (oral cavity 49.2%, oropharynx 31%, hypopharynx 30.3% and larynx 27.3%). In some tumors, the extent of genomic discordance argues against a monoclonal origin.
  
  
  CONCLUSIONS
  We demonstrate a high individual variation of intratumoral genomic heterogeneity depending on the localization and selection of matched pairs. These findings are of specific importance in view of establishing prognostic markers.
authors.affiliation: Department of Otolaryngology, Head and Neck Surgery, University Hospital Mannheim, Mannheim, Germany. karl.goette@hno.ma.uni-heidelberg.de
authors.forename: Karl
authors.initials: K
authors.lastname: Götte
authors.forename: Susanne C
authors.initials: SC
authors.lastname: Tremmel
authors.forename: Susanne
authors.initials: S
authors.lastname: Popp
authors.forename: Susanne
authors.initials: S
authors.lastname: Weber
authors.forename: Karl
authors.initials: K
authors.lastname: Hörmann
authors.forename: Claus R
authors.initials: CR
authors.lastname: Bartram
authors.forename: Anna
authors.initials: A
authors.lastname: Jauch
mesh_terms: D000368:Aged; D022981:Allelic Imbalance; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics* / Q000556:secondary; D002880:Chromosomes, Human, Pair 11; D002893:Chromosomes, Human, Pair 3; D002899:Chromosomes, Human, Pair 9; D004273:DNA, Neoplasm / Q000032:analysis; D005260:Female; D005784:Gene Amplification; D005819:Genetic Markers / Q000235:genetics*; D016678:Genome; D006258:Head and Neck Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008198:Lymph Nodes / Q000473:pathology*; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D009693:Nucleic Acid Hybridization; D016133:Polymerase Chain Reaction / Q000379:methods; D011379:Prognosis; D012494:Sampling Studies; D012680:Sensitivity and Specificity
chemical_list: D004273:DNA, Neoplasm; D005819:Genetic Markers