Siavosh Tabatabaeifar1, Martin J Larsen2, Stine R Larsen3, Torben A Kruse2, Mads Thomassen2, Jens A Sørensen4. 1. Department of Plastic Surgery, Odense University Hospital, Odense, Denmark; University of Southern Denmark, Institute of Clinical Research, Odense, Denmark. Electronic address: Siavosh.tabatabaeifar@rsyd.dk. 2. Department of Clinical Genetics, Odense University Hospital, Odense, Denmark; University of Southern Denmark, Institute of Clinical Research, Odense, Denmark. 3. Department of Pathology, Odense University Hospital, Odense, Denmark; University of Southern Denmark, Institute of Clinical Research, Odense, Denmark. 4. Department of Plastic Surgery, Odense University Hospital, Odense, Denmark; University of Southern Denmark, Institute of Clinical Research, Odense, Denmark.
Abstract
OBJECTIVES: Local recurrence and the development of second primary tumors (SPT) are important factors that can influence the survival rate of oral squamous cell carcinoma (OSCC) patients. We investigate the concept of field cancerization which proposes that normal tissue adjacent to the primary tumor harbor pre-neoplastic alterations that can lead to the development of local recurrence and SPTs. MATERIALS AND METHODS: To examine the concept of field cancerization, we applied whole-exome and targeted ultra-deep sequencing on 5 freshly frozen samples from a stage III OSCC patient from three tumor sites, lymph node metastasis and blood. Lastly, we sequenced one formalin-fixed paraffin-embedded recurrence biopsy that was collected approximately a year and half later located in the same area as before. RESULTS: Sequencing identified 126 somatic mutations. We identified 24 mutations in the recurrence biopsy and 14 mutations are shared by the primary tumor. CONCLUSION: The low number of shared mutations indicates that either these mutations represent a very early clone in the primary tumor's evolution, or that these mutations represent a pre-neoplastic field, in which the primary tumor and recurrence are derived from. In both instances, the clinical recurrence is of a monoclonal origin which suggests either field cancerization by migration of mutated cells in the adjacent mucosa, or that the recurrence developed out of remaining tumor tissue.
OBJECTIVES: Local recurrence and the development of second primary tumors (SPT) are important factors that can influence the survival rate of oral squamous cell carcinoma (OSCC) patients. We investigate the concept of field cancerization which proposes that normal tissue adjacent to the primary tumor harbor pre-neoplastic alterations that can lead to the development of local recurrence and SPTs. MATERIALS AND METHODS: To examine the concept of field cancerization, we applied whole-exome and targeted ultra-deep sequencing on 5 freshly frozen samples from a stage III OSCC patient from three tumor sites, lymph node metastasis and blood. Lastly, we sequenced one formalin-fixed paraffin-embedded recurrence biopsy that was collected approximately a year and half later located in the same area as before. RESULTS: Sequencing identified 126 somatic mutations. We identified 24 mutations in the recurrence biopsy and 14 mutations are shared by the primary tumor. CONCLUSION: The low number of shared mutations indicates that either these mutations represent a very early clone in the primary tumor's evolution, or that these mutations represent a pre-neoplastic field, in which the primary tumor and recurrence are derived from. In both instances, the clinical recurrence is of a monoclonal origin which suggests either field cancerization by migration of mutated cells in the adjacent mucosa, or that the recurrence developed out of remaining tumor tissue.