Genetics

[Susan Abis]

I have recently had genetic testing to rule out BRCA gene, but came up with a PTEN mutation (p.Y336... c.1008C>G)- tumor suppressant gene . I have a medical history of a tiny breast cancer about 12 years ago (a few millimeters), colon polyps, and macrocephaly. Other than that I am perfectly healthy.  My physicians have told  me I have Cowden syndrome, and it is now a 4 alarm fire with need for multiple tests per year, but all the studies I read on this indicate incidence is about 1/200,000. Not sure about the actual pathogenicity of this, as they are just reporting case studies and acknowledging there could be bias in diagnosis.  Anyone out there able to help me sort out the actual science of this?  Is the medical community getting out over their skis here?

genetics.pdf

[Arete]

Forgive me if this is too basic but; 

1. In order for a cell to become cancerous two main things need to happen; 1. Cell replication becomes uncontrolled and 2: Signals for cell apoptosis (programmed cell death) need to be ineffective. Cells have multiple failsafe mechanisms to prevent these, and all of them need to fail in order for a cell to become cancerous. 

2. PTEN encodes an enzyme (phosphatase) which regulates several cell functions, including apoptosis. Y336 is a nonsense mutation which introduces a premature stop codon, causing polymerase to stop transcribing the gene before it is fully done. This can render this enzyme ineffective/less effective for some or all of its functions. 

3. Having a somatic mutation such as Y336 in PTEN means that all of one's cells require fewer mutational steps to go from normal function to cancerous. There is therefore a greater global risk of the formation of cancer cell lines, and more frequent testing might be recommended by a physician. 

4. Having said mutation doesn't cause cancer on its own, nor means one WILL get cancer. It just means the risk is higher because one of the normal failsafes isn't in place. Compare it to a history of smoking, or similar. 

I hope that helps, and mods, delete if it crosses the line to medical advice.