Conditions such as Li Fraumeni Syndrome and other inherited cancer predisposition syndromes are associated with what are known as ‘germline’ DNA mutations. In other words mutations (mistakes, also called gene defects) in the DNA that people are born with rather than mutations which are specific to cancer cells. Many, if not most, cancer cells contain mutations in tumour suppressor genes such as TP53 and PTEN, but very few people are born with these mutations in all their cells.
In the past the conditions under which cancer patients would be tested for germline gene defects have been very confusing. This has been especially true in the case of TP53 testing. It’s important to be clear that we are not talking about testing cancer cells for specific gene defects but in testing for what ‘germline’ defects – in other words in testing normal tissue for evidence that the TP53 gene is damaged. While having a TP53 mutated in a tumour is not unusual, being born with a damaged TP53 gene is rare and potentially very dangerous.
The old rules for giving someone a TP53 test were very complicated and hard to follow. In consequence people who ought to have been tested were not. Things have improved in this respect, and Professor Nazneen Rahman and her colleagues at the Institute of Cancer Research Genetics and Epidemiology unit have come up with a much simplified testing and management protocol for TP53. The key points are that a test should be triggered by the following conditions:
An individual with:
- Adrenocortical cancer at any age
- Choroid plexus cancer at any age
- Rhabdomyosarcoma below 5 yrs
- Breast cancer below 30 yrs (if eligible for BRCA1/2 testing, this should be performed first)
- Two or more primary cancers of the following: sarcoma, breast, brain, adrenocortical or any childhood cancer; at least one below 46 yrs (with the exception of two breast cancers)
Two relatives affected with:
- Sarcoma, breast, brain, adrenocortical or any childhood cancer; one relative below 36 yrs and one relative below 46 yrs (with the exception of two breast cancers)
Three relatives affected with:
- Sarcoma below 45 yrs and
- any cancer below 45 yrs and
- any cancer below 45 yrs or sarcoma at any age
Note that not all TP53 defects are as dangerous as Li Fraumeni Syndrome, there are some defects which carry much lower risks of getting cancer than LFS. However, this is an area that needs much more research.
For more details please see:
If you are the parent of a child that meets the above criteria, or an adult who fits the bill, please show this protocol to your oncologist. At the very least you can have a discussion about whether to have the test or not.