About Me
Hallo everyone, my name is Jennifer Kluczny and I am a PhD student at the University Hospital in Düsseldorf. I started my Bachelors in Biochemistry and soon discovered my field of interest strongly lies in biomedical studies. During my Master’s program I had the opportunity to dip my toes into many different fields of biomedicine and it felt natural to continue into a PhD. Today I am proud to be part of the ENDEAVOR consortium, working on new developments in esophageal cancer research.
Why Barrett’s Esopahgus Matters
Barrett’s esophagus (BE) is a change in the lining of the esophagus (the food pipe): the normal flat cells are replaced by column-shaped cells more typical of the intestine. But why are we talking about Barrett’s esophagus? It is the only commonly recognized precursor to esophageal adenocarcinoma (EAC), the elevens most common cause of cancer globally and the seventh leading cause of cancer-related death1. Early-stage EAC often causes few or no symptoms, resulting in late-stage diagnosis and a poor overall survival rate.
Because most people with BE will not develop cancer, doctors face a dilemma: how to find the few that will progress without over-testing everyone? Today, BE is usually detected and regularly monitored by endoscopy (a camera-tube exam). This is costly and inconvenient. To address this, researchers such as myself are seeking better risk-stratification methods.
One of the EU-funded ENDEAVOR project aims is to define biomarkers that identify which BE patients are truly high-risk. The project combines minimally invasive sampling (for example, endoscopic brushing, a way to collect cells from the esophagus surface) with advanced molecular tests such as high-throughput technologies to develop a more precise risk score.
What do we mean by ‘High-Troughput Technologies’?
In plain language, high-throughput technologies are powerful lab methods that let scientists read large amounts of biological information quickly, for example, all the DNA in a sample, or gene activity across thousands of cells. These tools create big datasets that, when analysed, can spot patterns linked to progression and act as early warning signals.
Key types used in BE research include:
- 1. Single-cell sequencing: reads DNA or RNA from individual cells. This shows which specific cells carry certain mutations or abnormal gene activity.
- 2. Whole-exome or whole-genome sequencing (WES/WGS): reads either the protein- coding portion of the genome (exome) or the entire genome to reveal mutations across many genes.
- 3. Shallow whole-genome sequencing for copy-number profiling: a cost-effective way to detect large DNA gains or losses (copy-number alterations) across the genome
- 4. Spatial genomics / spatial omics: measures molecular changes and their position in the tissue, so you can see where potentially risky cells are located within the Barrett’s patch.
Zooming in: Clonal Diversity and Copy-Number Alterations (CNAs)
When there is long-term irritation, like in BE, the cells lining the esophagus can start to change. Some of these changes are harmless, but others can lead to cancer. Each time a cell changes, it becomes a little different from its neighbors, forming groups called “clones”. Clonal diversity means there are many such abnormal cell groups, and the more diverse they are, the higher the risk that some may eventually turn into cancer. Indeed, studies have shown that higher clonal diversity strongly predicts progression to cancer. In short, samples with a greater variety of cell clones were more likely to develop cancer than those genetically uniform ones2.
Another predictive signal is DNA copy-number alterations (CNAs). CNAs are gains or losses of large chunks of DNA (think of losing or duplicating pages in a book) and reflect genomic instability. A 2020 study showed that genome-wide copy-number profiles from routine biopsies predicted cancer up to a decade before clinical transformation3. That makes CNAs a promising early signal.
The current standard of operation uses so called FISH analysis (fluorescence in situ hybridization), a targeted, cell-level assay for a small number of genomic regions. However, FISH is labor- and time-intensive, and can only target a few specific genes.
How my PhD Project fits in
My doctoral work develops a single-cell sequencing pipeline that detects CNAs and maps clonal diversity at the level of individual cells collected from endoscopic brushes. I compare these single-cell results to traditional FISH and to bulk WES data from tissue biopsies. The aim is to test whether a single-cell approach can identify high-risk patients the same or more precisely than current tests, enabling earlier, personalized interventions.
Figure: Schematic overview of future risk stratification approach in Barret’s esophagus patients based on clonal diversity.
Implications for Patients and Future Outlook
For patients, these advances promise more personalized care. Instead of putting everyone with BE on the same surveillance schedule, a genomic test could sort patients by risk. High- risk patients would receive earlier treatment or more frequent monitoring, while low-risk patients could avoid needless procedures. This would improve quality of life and save healthcare costs.
Looking ahead, the field is rapidly advancing. High-throughput methods are becoming cheaper and more powerful and artificial intelligence may help combine genomic data with clinical records to improve risk predictions. All of this points toward a future of truly personalized Barrett’s surveillance, allowing more tailored care and earlier detection for the people who need it most.
Jennifer Kluczny
References
- Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024 May-Jun;74(3):229-263. doi: 10.3322/caac.21834. Epub 2024 Apr 4.
- Martinez P, Timmer MR, Lau CT, Calpe S, Sancho-Serra Mdel C, Straub D, Baker AM, Meijer SL, Kate FJ, Mallant-Hent RC, Naber AH, van Oijen AH, Baak LC, Scholten P, Böhmer CJ, Fockens P, Bergman JJ, Maley CC, Graham TA, Krishnadath KK. Dynamic clonal equilibrium and predetermined cancer risk in Barrett’s oesophagus. Nat Commun. 2016 Aug 19;7:12158. doi: 10.1038/ncomms12158.
- Killcoyne S, Gregson E, Wedge DC, Woodcock DJ, Eldridge MD, de la Rue R, Miremadi A, Abbas S, Blasko A, Kosmidou C, Januszewicz W, Jenkins AV, Gerstung M, Fitzgerald Genomic copy number predicts esophageal cancer years before transformation. Nat Med. 2020 Nov;26(11):1726-1732. doi: 10.1038/s41591-020-1033-y. Epub 2020 Sep 7.