What’s the tumour going to do?
ITS REALLY IMPORTANT TO KNOW HOW A TUMOUR WILL BEHAVE TO GIVE THE BEST TREATMENT.
HERE ADRIANA SARAIVA, TELLS US ABOUT SOME OF HER WORK IN TANIA SLATTER’S LABORATORY (see below), PATHOLOGY DEPARTMENT, DUNEDIN SCHOOL OF MEDICINE.
A molecular based brain tumour classification for better prediction of brain tumour outcome
Brain tumour is a solid mass of cells characterised by an abnormal and uncontrolled growth pattern. Depending on the cell origin, the tumour is classified as primary (starting in the brain) or secondary/metastatic. The brain metastases corresponds to cancer cells that escaped from its original locus (other part of the body), migrated, installed, infiltrated and now grows in the intracranial area. One in 4 patients with cancer may develop brain metastases. It has, typically, more aggressive outcomes with poor prognoses, requiring a quick and precise medical decision. The understanding of tumour subtypes is fundamental for an accurate diagnosis and to estimated prognosis and two find the an effective therapeutic approach.
Some tumours in the brain may be largely benign, having slow growth. The most common type is called Meningioma, which make up 30% of central nervous system tumours (incidence 6 per 100,000) and is 2.8 times more frequent in Māori. [1-3]. 20% patients have atypical lesions (WHO grade II) and have an unpredictable outcome, making them difficult to clinically management. A more accurate means to predict outcome for those with atypical meningiomas exists based on new molecular based technologies. These methods provide a better understanding of how tumours with similar morphology can behave differently to a treatment.
Meningioma project: The DNA methylation-base classification for meningioma has distinct ability to subtypes brain tumours and better predict longer-term overall survival compared to the current morphology based WHO grade (p= 0.0096) [1, 4-6]. This system has been designed with clinical practice in mind, with a pipeline for data analysis and subtype assignment. This project will adapt the molecular classification system for use in FFPE samples in New Zealand. The project will also determine if the subtypes are also relevant for Māori patients or if modified subtypes are required. This project is in collaboration with Dunedin and Hamilton hospitals.
Brain tumour Metastases project: Our group has found two new markers in brain tumour metastases that predict the severity and may aid the migration and development of tumours in the intracranial area. This project is in collaboration with Dunedin, Hamilton and Christchurch hospitals and a new collaboration with Queensland Australia. Work is underway to characterise the function of these markers to determine how they promote brain tumour metastases.
1) Sahm F, Schrimpf D, Stichel D, et al. DNA methylation-based classification and grading system for meningioma: a multicentre, retrospective analysis. Lancet Oncol. 2017. 18(5):682-694. doi: 10.1016/S1470-2045(17)30155-9.
2) Olson S, Law A. Meningiomas and the Polynesian population. ANZ J Surg. 2005. 75(8):705-9.
3) Wang D. The incidence of meningioma in the Midland region. Summer Studentship 2019. University of Auckland.
4) Karimi S, Zuccato JA, Mamatjan Y, et al. The central nervous system tumor methylation classifier changes neuro-oncology practice for challenging brain tumor diagnoses and directly impacts patient care. Clin Epigenetics. 2019. 11(1):185. doi:10.1186/s13148-019-0766-2.
5) Capper D, Jones DTW, Sill M, et al. DNA methylation-based classification of central nervous system tumours. Nature. 2018. 555(7697):469-474. doi:10.1038/nature26000.
6) Gkagkanasiou M, Ploussi A, Gazouli M, Efstathopoulous EP. USPIO-Enhanced MRI Neuroimaging: A Review. J Neuroimaging. 2016. 26(2):161-8. DOI: 10.1111/jon.12318
NZBTT inuagural grant award- $10,000
DR Tania Slatter, Department of Pathology,
Dunedin School of medicine
University of Otago.
On 04 September 2020 at our CARE/CURE/Couture Soiree at Olveston House Dunedin, we were proud to award our first grant to focus on brain tumour research. Tania has a distinguished career already and we can’t wait to see what comes next!
Tania’s goal is to understand how the mechanisms that regulate DNA damage lead to molecular changes that predispose to life-long health effects. For this research we use molecular and histo-pathological techniques in combination with collaborative clinical studies.
Specific projects in the laboratory are:
- Determining how telomere integrity is controlled in normal cells and how this changes with DNA damage. The goal of this study is to identify cancerous changes, or a predisposition to other diseases early.
- Identifying and characterising molecular sub-types of brain, breast, and other tumours to provide improved patient management and treatment options. This study identifies acquired and inherited genetic variants and then tests how these variants work toward tumour development, and whether these variants could be targeted for treatment.
- Investigating DNA damage to the placenta and how this affects fetal and maternal health outcomes. This study is part of the Otago Placental Study in collaboration with the Department of Women’s and Children’s Health.
- Investigating DNA damage in autoimmune disease and how this leads to further health complications.