Genetic Markers – Hope for New Brain Tumor Treatments

Researchers at The University of Nottingham have identified three sets of genetic markers that could potentially pave the way for new diagnostic tools for a deadly type of brain tumor that mainly targets children.

The study, published in the latest edition of the prestigious journal Lancet Oncology, was led by Professor Richard Grundy at the University’s Children’s Brain Tumour Research Centre and Dr Suzanne Miller, a post doctoral research fellow in the Centre.

It focuses on a rare and aggressive cancer called Central Nervous System primitive neuro-ectodermal brain tumors. Patients with CNS PNET have a very poor prognosis and current treatments, including high dose chemotherapy and cranio-spinal radiotherapy are relatively unsuccessful and have severe lifelong side-effects. This is particularly the case in very young children.

Despite the need for new and more effective treatments, little research has been done to examine the underlying causes of CNS PNET, partly due to their rarity. The Nottingham study aimed to identify molecular markers as a first step to improving the treatments and therapies available to fight the cancer.

The Nottingham team collaborated with researchers at the Hospital for Sick Kids in Toronto, Canada, to perform an International study collecting 142 CNS PNET samples from 20 institutions in nine countries.

Professor Richard Grundy said: “Following our earlier research we realised that an international effort was needed to bring sufficient numbers of cases together to make the breakthrough we needed to better understand this disease or indeed diseases identified in our study. The next step is to translate this knowledge into improving treatments.”

By studying the genetics of the tumors, they discovered that instead of one cancer, the tumors have three sub-types featuring distinct genetic abnormalities and leading to different outcomes for patients.

They found that each group had its own genetic signature through subtle differences in the way they expressed two genetic markers, LIN28 and OLIG2.

LIN28 OLIG2 Genetic Markers
Researchers identified the two genetic markers LIN28 and OLIG2 as a promising basis for more effective tools for diagnosing and predicting outcomes for young patients with CNS PNET brain tumors. Image adapted from University of Nottingham press release image.

When compared with clinical factors including age, survival and metastases (the spread of the tumors through the body), they discovered that group 1 tumors (primitive neural) were found most often in the youngest patients and had the poorest survival rates. Patients with group 3 tumors had the highest incidence of metastases at diagnosis.

Ultimately, the research has identified the two genetic markers LIN28 and OLIG2 as a promising basis for more effective tools for diagnosing and predicting outcomes for young patients with these types of brain tumors.

The research was funded by the Canadian Institute of Health Research, the Brainchild/Sick Kids Foundation and the Samantha Dickson Brain Tumour Trust.

Chief Executive of Samantha Dickson Brain Tumour Trust, Sarah Lindsell, said: “As the UK’s leading brain tumour charity, and the largest dedicated funder of brain tumour research, we are delighted that our investment has led to such significant success. It is great to see that understanding of these tumours is improving – this is desperately needed given the poor outcomes for children with this tumour. Samantha Dickson Brain Tumour Trust is proud to have been instrumental in this work.”

The Children’s Brain Tumour Research Centre is one of the projects set to benefit from the Impact Campaign, the biggest fundraising campaign in The University of Nottingham’s 130 year history. It aims to raise £150m to transform research, enrich the student experience and enable the institution to make an even greater contribution to the global communities it serves.

Contacts: Richard Grundy – Professor of Paediatric Neuro-Oncology at University of Nottingham
Emma Thorne – University of Nottingham
Source: University of Nottingham press release
Image Source: Image adapted from University of Nottingham press release image
Original Research: Abstract for “Markers of Survival and Metastatic Potential in Childhood CNS Primitive Neuro-Ectodermal Brain Tumours: an Integrative Genomic Analysis” by Daniel Picard, Suzanne Miller, Cynthia E Hawkins, Eric Bouffet, Hazel A Rogers, Tiffany SY Chan, Seung-Ki Kim, Young-Shin Ra, Jason Fangusaro, Andrey Korshunov, Helen Toledano, Hideo Nakamura, James T Hayden, Jennifer Chan, Lucie Lafay-Cousin, Pingzhao Hu, Xing Fan, Karin M Muraszko, Scott L Pomeroy, Ching C Lau, Ho-Keung Ng, Chris Jones, Timothy Van Meter, Steven C Clifford, Charles Eberhart, Amar Gajjar, Stefan M Pfister, Richard G Grundy, Annie Huang in Lancet Oncology Early Online Publication, 11 June 2012 doi:10.1016/S1470-2045(12)70257-7

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