BRCA test - Multisite vs Sequencing for Ashkenazi Jews

I have just tested positive to BRCA1 (68_69delAG or185delAG) gene. I understand that this gene is found in people of Askenazi jewish descent.I have 3 first cousins who have tested positive to this gene also as our DNA and gene mutation where crossmatched. The thing is my family's recent known genetic history does not include any Jewish relatives yet this gene and breast/ovarian cancer is very prevalent in my family. My mother and her sister must have both had this gene. My mother had both breast and ovarian cancer and three of her sisters had either breast or ovarian cancers at a young age. I have 4 first cousins who have had breast cancer at a very young age including one cousin who died at 38 after contracting breast cancer at 32. I also have great aunts and second cousins who contracted breast cancer at a young age.My mother used to talk about some Jewish ancestors but even so it is very odd that the gene is still so dominant in the the family's DNA considering all of the intermarriage that has gone on since.DNA and genetics are obviosuly very complicated.

I had the multi site 3 testing after I was Dx...it was negative...I asked the genetic counselor the likelihood of the full testing being positive she said that the multi-site 3 was where the mutation generally showed up in Askenazi Jews....as I was having a bilat, chemo, rads and ooph, my Tx would not be different if unfortunately, I had been positive....the difference would be for my daughters.

Why does the geneticist want you to have the full blown testing...what purpose does it serve?  Congrats on 10 years!

I agree with Helene...Sharsheret is a wonderful resource. 

Newalex, is your mutation the same one, called "187delAG"? It is common in India and Malaysia but probably very rare in mainland China...

Hi I am hoping someone will know this answer- since I won't get the results probably until next year due to the holiday.  As a Ashkenzi Jew with lots of BC in the family and LCIS atleast. I had testing and they just said that the 1st test in negative but waiting for the results of the 2nd. I signed for multi- ite- so does anyone know what I actually waiting for. BRCA 2?

thanks so much. Happy Holidays!

Hi,

I'm not used to surf in this fortum, but got link to this message from a friend that asked me to reply.

A disclosure: I am a genetic researcher that works in a private company in Israel, but I don't want to make advertisement to my company.

The first question is why you want to find the responsible mutation to BC (if exists). If you want to check your relatives (for examples., yout daughters) to know who is in a risk and should do breast examination often - this is a good reason.

But if you just want to know if you are have a hereditary risk to develop cancer again, it is not a good reason. I will explain: if the tests will find a mutation known as responsible to cancer, you will know that you are in a risk, and should be examined often. But if all genetic tests are negative, this does not promise that you are not a carrier of a mutatin that have not been checked! There are many mutations that may cause to cance, only part of them have been identified thus far by scientists. So it is simpler for you (if you do not have daughters) to not do the test, and just examine your breast and ovaries soon, every 6 month or even less.

Regardind sequencing of the BRCA genes in Ashkenazi Jewish women: only a few percentages  (~3.5%) of Ashkenazi women with breast cancer have a BRCA mutation. 90$ of these mutations are the 3 mutations that you most probably checked. So the chance that you have another BRCA mutation that deserves an expensive sequencing of the whole two genes is low, and I would not recommend to do this test. By the way, when you consider which genetic tests to do, it is much better to consult with a genetic advisor/clinician and not with a physician. Today we know that only ~20% of Ahkenazi women that surely have hereditary breast cancer (because 3 or more women in the family had the disease) - have BRCA mutations, and 90% of the are 3 common mutations. This means that the other 80% women with BC have mutations in other genes! There are 44 genes that have been linked with BC thus far, but in the "old" method of sequencing, it is very expensive and not practical to sequence all of them.

A new generation technology for sequencing have been developed during the  last years, and begins entering to the clinical diagnostic tests. Several companies today develop tests, based on the new technology, that will sequence many genes in parallel, at the same cost as the seqeuncing of BRCA alone today.

So if it is not urgent for you, I would recommend that you will wait for about 6 months until  new generation sequencing of all the BC genes will be available, and do this test instead of sequencing BRCA1and BRCA2 alone.

I  hope I helped.

Have a happy and healthy new year!