Background
Intra-tumor heterogeneity (ITH) refers to the coexistence of molecularly distinct clones within a tumor. It is a major obstacle in cancer management due to its association with poor prognosis and therapeutic resistance. Esophageal adenocarcinoma (EAC) shows pronounced ITH, with distinct genomic alterations found in different tumor regions. Some of these alterations allow subclones to survive treatment, leading to tumor recurrence. While genomic ITH in EAC has been documented, contribution of epigenetic changes – especially DNA methylation patterns – remains understudied. A better understanding of the epigenetic ITH in EAC is therefore needed for advancing patient care.
Project Overview and Aims
DNA methylation analysis of multiple tumor regions provides a more complete picture of ITH and may offer opportunities to discover clinically relevant epigenetic biomarkers. Biomarkers that are consistently methylated across tumor regions (homogeneous) are less affected by sampling bias. These biomarkers can be of value for improving prognostication and providing insights into therapy resistance.
Bioinformatic analysis of genome-wide DNA methylation data from multi-regional EAC samples is currently on-going in our group. Relevant genome regions will require experimental validation to translate them into clinically applicable biomarkers.
This master’s project aims to a) provide an overview of the literature addressing ITH in EAC and b) experimentally validate DNA methylation biomarkers with potential to improve prognostication and provide insights into therapy resistance.
Your Role as a Master’s Student:
As a Master’s student, you will develop a strong background in Molecular Biology and gain hands-on experience with key laboratory techniques applied to clinical cancer research. Your main tasks will include:
- Familiarization with clinical sample handling: Learn about the processes involved in patient sample preparation as well as biobank and clinical database management.
- Assay design: Design DNA methylation assays targeting candidate biomarkers.
- Laboratory techniques: Perform bisulfite conversion and droplet digital PCR (ddPCR) to analyse DNA methylation biomarkers.
- Data analysis: Analyse experimental data to evaluate the performance and clinical relevance of the biomarkers.
- Collaborative research: Work closely with a national, multidisciplinary expert group in esophageal cancer (NORECa), including oncologists, surgeons and pathologists.
Research environment:
The project will be carried out in the Lind lab of Epigenetics, at The Department of Molecular Oncology, Institute for Cancer Research, Oslo University Hospital. Our department has a strong focus on student training and mentorship, and co-supervisor Guro E. Lind coordinates the integrated MSc and PhD course BIOS5710/9710 Advanced Cancer Biology. You will be trained alongside another Master’s student, and work as part of an interdisciplinary team in a collaborative and supportive environment. You can read more about the Lind lab here: OUH - Epigenetics Group (Lind).
Supervision:
Rita Pinto (Researcher, main supervisor) and Guro E. Lind (Professor, Epigenetics group leader; co-supervisor and internal supervisor at IBV).
If you find this project interesting or have any questions, please contact Rita Pinto (ritap@ous-research.no).