title: Control region mutations and the 'common deletion' are frequent in the mitochondrial DNA of patients with esophageal squamous cell carcinoma.
abstract: BACKGROUND
  North central China has some of the highest rates of esophageal squamous cell carcinoma in the world with cumulative mortality surpassing 20%. Mitochondrial DNA (mtDNA) accumulates more mutations than nuclear DNA and because of its high abundance has been proposed as a early detection device for subjects with cancer at various sites. We wished to examine the prevalence of mtDNA mutation and polymorphism in subjects from this high risk area of China.
  
  
  METHODS
  We used DNA samples isolated from tumors, adjacent normal esophageal tissue, and blood from 21 esophageal squamous cell carcinoma cases and DNA isolated from blood from 23 healthy persons. We completely sequenced the control region (D-Loop) from each of these samples and used a PCR assay to assess the presence of the 4977 bp common deletion.
  
  
  RESULTS
  Direct DNA sequencing revealed that 7/21 (33%, 95% CI = 17-55%) tumor samples had mutations in the control region, with clustering evident in the hyper-variable segment 1 (HSV1) and the homopolymeric stretch surrounding position 309. The number of mutations per subject ranged from 1 to 16 and there were a number of instances of heteroplasmy. We detected the 4977 bp 'common deletion' in 92% of the tumor and adjacent normal esophageal tissue samples examined, whereas no evidence of the common deletion was found in corresponding peripheral blood samples.
  
  
  CONCLUSIONS
  Control region mutations were insufficiently common to warrant attempts to develop mtDNA mutation screening as a clinical test for ESCC. The common deletion was highly prevalent in the esophageal tissue of cancer cases but absent from peripheral blood. The potential utility of the common deletion in an early detection system will be pursued in further studies.
authors.affiliation: Cancer Prevention Studies Branch, Center for Cancer Research, National Cancer Institute, Bethesda, MD 20892, USA. abnetc@mail.nih.gov
authors.forename: Christian C
authors.initials: CC
authors.lastname: Abnet
authors.forename: Konrad
authors.initials: K
authors.lastname: Huppi
authors.forename: Ana
authors.initials: A
authors.lastname: Carrera
authors.forename: David
authors.initials: D
authors.lastname: Armistead
authors.forename: Keith
authors.initials: K
authors.lastname: McKenney
authors.forename: Nan
authors.initials: N
authors.lastname: Hu
authors.forename: Ze-Zong
authors.initials: ZZ
authors.lastname: Tang
authors.forename: Philip R
authors.initials: PR
authors.lastname: Taylor
authors.forename: Sanford M
authors.initials: SM
authors.lastname: Dawsey
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000453:epidemiology / Q000235:genetics*; D002681:China / Q000453:epidemiology; D002872:Chromosome Deletion; D022801:Complementarity Determining Regions / Q000235:genetics; D004272:DNA, Mitochondrial / Q000032:analysis*; D004273:DNA, Neoplasm / Q000032:analysis*; D004938:Esophageal Neoplasms / Q000453:epidemiology / Q000235:genetics*; D006801:Humans; D015994:Incidence; D019901:Locus Control Region / Q000235:genetics*; D005810:Multigene Family; D009154:Mutation; D017354:Point Mutation; D011110:Polymorphism, Genetic; D012016:Reference Values; D015996:Survival Rate
chemical_list: D022801:Complementarity Determining Regions; D004272:DNA, Mitochondrial; D004273:DNA, Neoplasm