December 5, 2013 at 3:14 pm #359Wot53Participant
I am not diagnosed with LFS but am investigating the connection between TP53 Mutations in tumours and whether the type of mutation can indicate LFS or not.
I was wondering if everyone/anyone in this forum with LFS knows the type of TP53 mutation(s) that they have or otherwise runs in their family? Eg R337H appears the most frequent based on the iarc tp53 database.
Was also interested whether it is the one mutation type that is passed down, or whether the mutations can differ, albeit still within the TP53 Gene?
If other mutations outside TP53 are also commonly found?
If testing of any tumors always show the same TP53 Mutations?
And lastly given there is 2 copies of the gene, whether it is common to have one mutated and one normal (wild type), one mutated and the other deleted, or both mutated?
This forum is a great resource and I hope answers to the above can provide further help and insights.
WotsyDecember 6, 2013 at 12:56 pm #360PanKeymaster
That’s an interesting set of questions! Normally when someone has a TP53 gene test and it comes back with a diagnosis of LFS the particularly mutation will be listed so in families with multiple members carrying the diagnosis it should be possible to check that it’s the same mutation. Based on my understanding of the research, it normally is the same mutation that is passed down through the generations in a families.
In answer to your last question: most LFS patients are heterozygous – they have one normal and one mutated TP53 gene. There are some individuals who are homozygous (two mutated TP53 genes), but this is very rare (and it’s rare that someone with both genes mutated survives long enough to pass it on the descendants).
The other thing to note is that – as I understand it – most LFS patients do not have cancers where both copies of the TP53 gene are deleted or mutated. This is somewhat surprising, but it’s most likely that the mutated gene has some ‘gain of function’ that provides the tumours with survival advantages.
Can I ask what’s behind the questions? I’m intrigued.
PanDecember 8, 2013 at 5:08 pm #363Wot53Participant
Thank you for the reply and information.
In my family there was a case of childhood cancer, which in the tumour analysis showed a R280K P53 Mutation in one allele and a deletion of the other. The only other case was Melanoma a couple of generations prior but this had no analysis done.
I appreciate analysis of tumours often show mutations that are only in the tumour, however any mutation in P53 raises the question whether it is linked to LFS.
My investigations have not shown a lot of information about the types of P53 mutations that happen with LFS, other than what I found in the COSMIC and iarc databases. Most published articles do not include very much detail on this, nor do they tend to explain the combinations or if it is always the same type of mutation that is passed through the families, or shows in the various cancers that (unfortunately) can happen.
It was also of interest whether the deletion of one allele and retention of normal wild type for the other allele was common or not, and whether this tended to be less problematic than mutation/wild combinations or not.
For many people I suspect they have not looked at the mutation type level but was hoping some may have and that gathering some data here might shed some light.
WotsyDecember 14, 2013 at 10:59 pm #381PaulWParticipant
Pan, I was really struck by your comment:
[quote=”pan” post=294]The other thing to note is that – as I understand it – most LFS patients do not have cancers where both copies of the TP53 gene are deleted or mutated. This is somewhat surprising, but it’s most likely that the mutated gene has some ‘gain of function’ that provides the tumours with survival advantages.
I’d be really interested in any links to research papers that have more information on this if you have any?
Paul.December 14, 2013 at 11:40 pm #382PanKeymaster
Paul, I got that from a discussion with Professor Nazneen Rahman at the Institute of Cancer Research. But it’s an interesting point worth a bit of additional research I think, so I’ll take a look to see what I can find. I know you’ll do the same, so if you do come up with any references can you post them here?
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