The Subclonal Structure and Genomic Evolution of Oral Squamous Cell Carcinoma Revealed by Ultra-deep Sequencing

Siavosh Tabatabaeifar, Mads Thomassen, Martin Jakob Larsen, Stine Rosenkilde Larsen, Torben A Kruse, Jens Ahm Sørensen

Research output: Contribution to conference without publisher/journalConference abstract for conferenceCommunication


Background: Oral squamous cell carcinoma (OSCC), a subgroup of head and neck squamous cell carcinoma (HNSCC), is primarily caused by alcohol consumption and tobacco use. Recent DNA sequencing studies suggests that HNSCC are very heterogeneous between patients; however the intra-patient subclonal structure remains unexplored due to lack of sampling multiple tumor biopsies from each patient.
Materials and methods: To examine the clonal structure and describe the genomic cancer evolution we applied whole-exome sequencing combined with targeted ultra-deep targeted sequencing on biopsies from 5stage IV OSCC patients. From each patient, a series of biopsies were sampled from 3 distinct geographical sites in primary tumor and 1 lymph node metastasis. A whole blood sample was taken as the matched reference.
Results and discussion: Our results demonstrate that ultra-deep sequencing gives a level of unprecedented high resolution enabling clear detection of subclonal structure and observation of otherwise undetectable mutations. Furthermore, we demonstrate that OSCC show a high degree of inter-patient heterogeneity but a low degree of intra-patient/tumor heterogeneity. However, some OSCC cancers contain complex subclonal architectures comprising distinct subclones only found in geographically distinct regions of the tumors. The metastatic potential of the tumor is acquired early in the tumor evolution, as indicated by the lymph node sharing the majority of the mutations with the tumor biopsies, while rarely acquiring novel mutations that are specific for the metastasis.
Conclusion: Ultra-deep sequencing of multiple biopsies from OSCC and metastasis enables detection of subclonal structure and genomic evolution. The metastatic potential of OSCC is acquired early in the tumor evolution, and our results indicate that the tumor may not need to acquire additional alterations for it to be able to metastasize and adapt to its new lymph node surroundings.
Original languageEnglish
Publication date3. Jun 2016
Publication statusPublished - 3. Jun 2016
EventDSPR Forårsmøde 2016 - Panum, København, Denmark
Duration: 3. Jun 20163. Jun 2016


ConferenceDSPR Forårsmøde 2016


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