Sequencing TSCC

Dnr:

SNIC 2016/3-64

Type:

SNAC Small

Principal Investigator:

Karin Nylander

Affiliation:

Umeå universitet

Start Date:

2016-10-18

End Date:

2017-11-01

Primary Classification:

30499: Annan medicinsk bioteknologi

Webpage:

Allocation

Abstract

Squamous cell carcinoma of the tongue, TSCC, is a severe disease with an increasing incidence worldwide, including young people (≤40 years) and particularly women. Patients with oral cancer, of which the tongue is the major site, often have molecular changes in clinically normal mucosa surrounding the tumour, the so-called “field effect” or “field cancerization”. Patients treated for oral carcinoma thus run a risk of developing a relapse within the same area or a new tumour in the vicinity. The present project aims at mapping changes specific for the clinically tumour free field surrounding the tongue tumour. These field cancerization abnormalities could identify the alterations that are responsible for tumour initiation and therefore, at least theoretically, could represent targets for eradicating both pre-existing tumours and the potentially pre-neoplastic cells that are responsible for relapse. Furthermore, differences/similarities between TSCC in young (≤40 years) and old (>65 years) patients will be mapped. In this project we will use TSCC, clinically tumour free tissue adjacent to the TSCC and blood from the same patients. Tumour tissue and clinically tumour free tissue adjacent to the tumour will be used for whole-genome gene expression profiling and DNA and RNA from the same samples plus blood (to look for germ line mutations) will be further analysed using whole exome and whole transcriptome sequencing. The field cancerization changes we find can either be an effect of the already established tumour on the non-neoplastic surrounding tissue, or can represent changes that precede development of a new tumour. Whether these alterations in apparently normal tongue tissue are cause or effect of the accompanying TSCC, they represent aberrations from normal tongue tissue indicative of tumour formation or tumour presence. The comparison between young and old patients will clarify if there are differences at the expression or genetic level that can help explain the increasing number of young patients being affected by this severe and mutilating disease. The project is carried out in collaboration with ENT-specialists, and all studies are performed on tissue from patients with TSCC, and results thus mirror the clinical reality. As among collaborators there are experienced clinicians, results can be professionally evaluated concerning their clinical significance, and findings of clinical impact can also be quickly implemented in the clinical practice.