Genetic relationship between multiple squamous cell carcinomas arising in the oral cavity

Head Neck. 2014 Jan;36(1):94-100. doi: 10.1002/hed.23259. Epub 2013 Apr 30.


Background: Histological and clinical criteria are generally used to differentiate second primary tumors (SPTs) from local recurrences. The purpose of the present study was to apply mitochondrial DNA (mtDNA) D-loop analysis to differentiate SPTs from local recurrences and to validate the clinical classification.

Methods: The study population consisted of 20 consecutive patients presenting multiple oral neoplastic lesions for a total of 25 paired lesions. The mtDNA D-loop analysis was performed by direct sequencing and phylogenetic clusterization.

Results: Agreement between mtDNA analysis and clinical classification was found in 19 cases. Discrepancies arose in 6 cases in which the clinical criteria based only on the spatial or temporal distance of the second lesion from the index tumor had led to a diagnosis of SPT (2 cases) or local recurrence (4 cases).

Conclusion: The present data highlight the value of mtDNA analysis in establishing the clonal relationship between the index tumor and the second neoplastic lesion.

Keywords: clonality; mitochondrial DNA D-loop; multiple tumors; oral cancer; second primary tumor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / surgery
  • Cohort Studies
  • DNA Mutational Analysis
  • DNA, Mitochondrial / genetics*
  • Female
  • Follow-Up Studies
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Middle Aged
  • Mouth Neoplasms / genetics*
  • Mouth Neoplasms / pathology
  • Mouth Neoplasms / surgery
  • Neoplasm Recurrence, Local / genetics*
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / surgery
  • Neoplasms, Second Primary / genetics*
  • Neoplasms, Second Primary / pathology
  • Neoplasms, Second Primary / surgery
  • Retrospective Studies
  • Risk Assessment


  • DNA, Mitochondrial