Related Experiment Video
Updated: Jun 12, 2025
Intramucosal Inoculation of Squamous Cell Carcinoma Cells in Mice for Tumor Immune Profiling and Treatment Response Assessment
Published on: April 22, 2019
Genomic alterations in the stepwise progression from normal mucosa to metastasizing oral squamous cell carcinoma
Jakob Myllerup Jensen1, Sannia Mia Svenningsen Sjöstedt1,2,3, Javiera Laing Carmona4
1Department of Otorhinolaryngology, Head and Neck Surgery and Audiology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.
Introduction:
The aim of this study was to investigate the genomic changes that occur in the development from dysplasia, cancer and to regional metastases in patients with oral cavity squamous cell carcinoma (OSCC).
Material And Methods:
We included OSCC patients with lymph node metastases at diagnosis, treated with primary surgery at Rigshospitalet, University of Copenhagen in the period 2007-2014. The resected tumor specimens were evaluated by a pathologist, who marked areas of morphologically normal tissue and dysplasia surrounding the cancer, two areas from the cancer tissue, and one area within the lymph node metastases. From these areas a punch biopsy was taken, and DNA from each sample was extracted and sequenced using Illumina's TSO500 HT cancer panel.
Results:
From 51 OSCC patients, 255 samples were included, comprising a wide variety of genomic alterations. Substantial intratumor heterogeneity was found. The most commonly mutated gene was TP53, mutated in 65% of all samples. Only two patients had no TP53 mutation in any samples. We found that morphologically normal appearing mucosa as well as surrounding dysplasia also contained malignant mutations, supporting the theory of field cancerization. There was a significant lower average tumor mutational burden (TMB) in the lymph node metastases compared to the primary tumors, supporting the theory of clonal selection.
Conclusion:
Substantial inter- and intratumor genomic heterogeneity was found. Mutation of TP53 was the most common and was present in all but two patients. Our data strongly supports the theory of clonal selection and the theory of field cancerization.
Related Concept Videos
02:07Tumor Progression
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
02:21Cancers Originate from Somatic Mutations in a Single Cell
02:30Metastasis
Epithelial-to-Mesenchymal Transition
The epithelial-to-mesenchymal transition or EMT is a developmental process commonly observed in wound healing, embryogenesis, and cancer metastasis. EMT is induced by transforming growth factor-beta (TGF-β) or receptor tyrosine kinase (RTK) ligands, which further...
02:53Adaptive Mechanisms in Cancer Cells
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
01:33Cancer-Critical Genes I: Proto-oncogenes
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...