Over the last year my project has morphed and the research aims have been redirected – as is the nature of a PhD project. The good news is that my research question is now a lot more focused, and we are using a relatively new (and successful) approach to identify novel sarcoma genes. The redirection of the project has also resulted in an exciting collaboration with Professor David Thomas from the Kinghorn Cancer Centre in Sydney and the International Sarcoma Kindred Study.
The broad aim of the study is to identify new genetic variants that may predispose individuals for sarcoma. To do this, we will be looking at cancer cluster families (families with multiple occurrences of cancer, especially sarcomas) to find out what genetic mutations are causing cancer, and whether these might be novel genes for causing sarcomas.
For the first aim of the study we will look closely at three cancer cluster families from the International Sarcoma Kindred Study using whole exome sequencing. Whole exome sequencing gives us the genetic information for all the regions of the DNA sequence that encodes proteins.
In the second aim we will use what we know about inheritance patterns in families to filter out any rare mutations that could be causing cancer in these families. We will pick out the best five mutations from these families to investigate in a larger cohort. In the third aim we will look for the five mutations (identified in Aim 2) in 500 sarcoma cases and 500 control participants to see if any of the mutations we found in the families are present in unrelated sarcoma cases.
Just this week the DNA samples for Aim 1 have arrived in Perth and my goal is to have the families sequenced by the end of the year. The next phase of the project will be to analyse the exome sequences using supercomputers to identify which genetic changes might be associated with sarcoma.
To give you an idea about the size of the data we will generate: each exome consists of 30 million base pairs (data points) and I will be sequencing 21 exomes from family members, plus 5 tumour exomes. That works out to be about 780,000,000 data points! It is going to be a busy start to the new year!
