Annual research report: chromosome 1p and 19q deletion analysis

	2006	2005	Press Release

Implementation and audit of chromosome 1p and 19q deletion analysis for guiding the treatment of patients with malignant brain tumours

Progress report May 2006

Background
Deletions of chromosomes 1p and 19q occur in a high proportion of oligodendrogliomas, including over half of those that are anaplastic. The combination of these deletions has been reported to predict a higher response rate to PCV chemotherapy and prolonged subsequent survival. 1p and 19q deletions are observed in a small proportion of other malignant glial tumours, particularly glioblastomas. The predicted value of these deletions in glioblastomas is still uncertain. For over 3 years now, we have now been performing 1p and 19q deletion analysis on malignant glial tumours from patients undergoing neurosurgery at Frenchay Hospital. Our aims are (i) to use the test to optimise patient’s quality as well as quantity of life, (ii) to ascertain the predictive value of isolated or combined 1p or 19q deletions in patients with all forms of malignant glial tumour in relation to treatment with PCV, Temozolomide and irradiation.

Work to date
Since the commencement of this study, we have analysed blood and tumour tissue from over 120 patients. Assessment of deletion of chromosome 1p and 19q has been made by loss of heterozygosity analysis, in which tumour DNA has been compared to normal DNA obtained from a blood sample. Multiplex PCR has been used to amplify DNA from four microsatellite repeat regions on chromosome 1p and four on 19q (D1S468, D1S214, D1S2736, D1S199, D19S5408, D19S412, D19S926 and D19S418). Of the tumours we have assessed, 62% have shown no loss of heterozygosity, 24% have shown deletion of both 1p and 19q, 6% have shown deletion of 1p only and 8% have shown deletion of 19q only. All patients with anaplastic oligodendrogliomas whose tumours have shown 1p and 19q deletions have been offered PCV chemotherapy. No patient has been denied a trial of PCV at the time of relapse but the early use of this chemotherapy has been discouraged for patients whose chance of benefit is low. All patients may be offered temozolomide as second line treatment, in accordance with national guidelines.

Ongoing work
We propose to continue to perform 1p and 19q analysis and to collect data over the next 12 months. During this time we will, in addition, perform a detailed analysis of all our collected data, with the aims of establishing the relationship between the 1p and 19q deletion profile and (i) response to radiotherapy, (ii) response to PCV, and (iii) response to Temozolomide. We shall also examine the relationship of the deletion profile and responsiveness to therapy to the histological subtype of the tumour, the age and sex of the patient, the location of the tumour, the pre-treatment clinical performance score and the extent of neurosurgical resection. We hope that this information will help us to secure funding from PCTs for the incorporation of this service into the routine management of all patients with malignant glial tumours.

Acknowledgement
All staff involved in this work remain extremely grateful to Hammer Out for their continued support of this project. We are now one of the most experienced centres in the UK in providing this service and this would not have been possible without the support of Hammer Out.