Research Report 2004 – Molecular Oncology Laboratory

Congratulations to Dr Elizabeth Algar and her team on having her laboratory fully accredited by NATA for the leukaemia and solid tumour testing that they undertake. The auditors were very complimentary about the way the lab was set up and the methods being used.

The laboratory has been installed primarily by Dr. Elizabeth Algar with occasional technical assistance from Gerlinda Amor. The major focus of the year has been to obtain accreditation for the tumor testing that the laboratory has established. The laboratory was reviewed by NATA in June and formally accredited in November. In addition Dr. Algar has recently applied for accreditation with the Human Genetics Society of Australasia (HGSA) which will enable her to formally sign off on diagnostic test results. To date thirteen tests for paediatric solid tumors and tumor syndromes have been established and accredited. The laboratory has participated in two external quality assurance programs run by the Royal College of Pathologists of Australasia (RCPA) and the HGSA. This is the first step towards establishing the CCC as a centre for paediatric tumor testing.

Dr. Algar has supervised a graduate student in the lab, Anita Sridhar, who undertook a preliminary study of DNA methyltransferase genes in Beckwith Wiedemann Syndrome to test whether abnormalities in these genes may cause the DNA methylation and chromosomal abnormalities in the syndrome. The results that Anita generated are promising, and were presented at the American Society for Human Genetics meeting in Toronto in October by Dr. Algar. This study is worthy of completion as we have found some evidence suggestive of the involvement of these genes in the Beckwith Wiedemann Syndrome. Beckwith Wiedemann is a syndrome in which one in ten children will develop a solid tumor. These tumors are typically Wilms’ tumours and hepatoblasomas, however rhabdomyosarcomas and neuroblastomas have also been reported. Therefore this research is relevant to the development of these tumors as well.

One observation Dr. Algar has made as a result of the genetic analyses she has performed on Beckwith Wiedemann Syndrome patients is that certain distinct chromosomal or DNA changes are linked to the development of particular tumor types. This information is therefore relevant to our understanding of how these tumors may have developed and opens up new avenues for investigation.

Dr. Algar was involved in a collaborative study examining whether children conceived by IVF procedures were more likely to be affected by Beckwith Wiedemann Syndrome as compared with the non-IVF population. We found a statistically significant (nine-fold) increase in the incidence of BWS in children conceived by IVF in Victoria, which was in agreement with similar studies performed overseas, however our study was more statistically rigorous than previous studies. The study was published in the high profile American Journal of Human Genetics in September. These findings suggest the possibility that environmental factors may contribute to the altered chromosomal methylation patterns that are associated with BWS and this is an area worthy of further investigation.

Dr. Algar was recently invited to be part of the program committee for an international conference on the Wilms’ tumor gene (WTI) to be held in Kyoto Japan in October of 2005. The WTI gene is not only involved in the development of Wilms’ tumor but also in the development of leukaemias. Dr. Algar has previously examined the role of the gene in the development of these cancers and more recently in neuroblastoma and brain tumors. Recent work by overseas research groups has shown that WTI may also play a role in breast, ovarian and oesophageal cancers. A Japanese group has undertaken some exciting work showing that the WT1 gene may be specifically targeted using immunotherapy, and in animal models of leukaemia the disease regressed following immunization with a portion of the WTI protein. Human clinical trials using this approach are now being conducted on leukaemia and solid tumor patients in Japan. Bringing together people at the WTI meeting, who have an interest in this field, may lead to fruitful areas of investigation and new therapies.