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Reconstructing oral cavity tumor evolution through brush biopsy.

Evit John1, Tom Lesluyes2, Toby M Baker1,2

  • 1Department of Genetics, The University of Texas MD Anderson Cancer Center, 1400 Pressler St, FCT 10.6008, 77030, TX, Houston, USA.

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Non-invasive brush biopsies can accurately capture the genomic profile of oral potentially malignant disorders (OPMDs) and oral squamous cell carcinoma (OSCC). This method reveals shared genomic alterations, indicating common origins and divergent evolution between OPMD and OSCC lesions.

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Area of Science:

  • Genomics
  • Oral Pathology
  • Cancer Evolution

Background:

  • Oral potentially malignant disorders (OPMDs) with genomic alterations progress to oral squamous cell carcinoma (OSCC).
  • Genomic profiling typically requires invasive tissue biopsies.
  • The utility of non-invasive brush biopsies for OPMD genomic landscape analysis is unclear.

Purpose of the Study:

  • To assess the accuracy of brush biopsy in reconstructing the genomic profile of OPMD and OSCC.
  • To investigate the potential of brush biopsy in understanding tumor evolution in paired OPMD and OSCC lesions from a single patient.

Main Methods:

  • Analysis of single nucleotide variants (SNVs), copy number aberrations (CNAs), and subclonal architectures.
  • Comparison of paired tissue and brush biopsy samples from OPMD and OSCC lesions.
  • Assessment of genomic alterations in normal buccal mucosa for specificity.

Main Results:

  • Brush biopsies captured 90% of SNVs and showed comparable CNA profiles to tissue biopsies.
  • Genomic alterations identified in brush biopsies were specific to lesions, not present in normal mucosa.
  • Shared SNVs and CNAs between OPMD and OSCC lesions indicated a common ancestral origin, confirmed by subclonal reconstruction.

Conclusions:

  • Brush biopsy is a viable non-invasive method for accurate genomic profiling of OPMD and OSCC.
  • This technique provides insights into the shared ancestry and divergent evolution of oral lesions.
  • Brush biopsies can aid in understanding tumor progression and reconstructing oral cancer evolution.