loss of a single (of two copies) of a tumor suppressor gene enough to flip bc "switch

[Lani]

Tumor suppressor tips the balance in breast cancer development

MedWire News: Loss of the tumor suppressor gene Tip60 is associated with the development of aggressive breast tumors, a discovery that could have important implications for how certain breast cancers are treated in the future, reveals an international team of researchers.

"We suggest that this is because critical levels of Tip60 are required for mounting an oncogene-induced DNA-damage response (DDR) in incipient tumor cells, the failure of which might synergize with p53 mutation towards tumor progression," the researchers explain

Chiara Gorrini (European Institute of Oncology, Milan, Italy) and colleagues found that Tip60 messenger (m)RNA levels were significantly reduced in 21 of 52 ductal breast carcinomas and 17 of 20 high-grade tumors, relative to matched normal tissue.

The researchers also measured TIP60 protein in an additional 179 breast cancers using immunohistochemistry on tissue microarrays. In 129 (72%) cases there was no TIP60 protein in the cell nucleus, whereas in normal breast tissue most of the protein was localized in the cell nucleus.

The proportion of cancers lacking nuclear TIP60 protein was even higher in aggressive cancers, with over 70% of grade 2, and over 90% of grade 3 tumors negative for TIP60.

Reporting their findings in the journal Nature, the researchers suggest that defects in the Tip60 gene appear at an early stage of breast cancer development and predispose women to aggressive tumors.

Co-author Tim Crook (Breakthrough Breast Cancer Research Centre, London, UK) commented: "The identification of Tip60's role in breast cancer is a step towards predicting the aggressiveness of the disease and then individualizing chemotherapy for women."

He added: "If we can transfer this knowledge to the clinic, it could have dramatic effects."

The study also found that, unlike most tumor suppressors, the Tip60 gene only needs to have one copy altered to stop functioning properly. The researchers suggest that critical levels of TIP60 are required for it to perform its vital role in DDR in incipient tumor cells.

Antonia Dean, a Clinical Nurse Specialist from the UK charity Breast Cancer Care, emphasized the need for further studies to fully determine how these findings can be translated into practical benefits for people with breast cancer.



Nature 2007; 488: 1063-1067

http://www.nature.com/nature/journal...ture06055.html

[Lani]

but her2 not mentioned (?not tested)

[TSund]

Is this factor testable? Is it included in the oncogene test?

[Lani]

the answer is no, it is not one of the factors that make up the recurrence score.

It can be tested for, hence the study--don't know of testing that is clinically available (ie, outside of research) or FDA approved (hence reimbursable)

[Jean]

Identifying this new Gene could open doors for treatment...this new finding further proves how much we need to discover the role of genes
in bc and recurrance - this could explain why some bc patients do well
without chemo depending on their genes. There is much to be understood
and learning how bc will respond to treatment - there are so many changes that take place in bc cells - let's hopet his new gene will help
hit the target....

Each day we get a little bit closer.....
Jean

[Lani]

responsible for her2+ bc (it may not be the only one) and it was Xlinked so that only one copy was necessary to cause the disease. They same gene is necessary for T regulatory cells (the ones which help her2+ breast cancer hide from the immune system) Interestingly, this gene seemed especially linked to her2+ ER+ breast cancer, a group of breast cancers (probably several when it all comes down to it) for which they are having a hard time designating a molecular subtype of bc --as best I can ascertain ~30% of luminal Bs are her2+ ER+. The gene is called FOXP3 and its absence allows
amplification of her2. Use the search funciton and put in FOXP3 if you missed my earlier post.

Hope this helps...

[Jean]

hmmm thanks Lani did miss that post will check it out!

Jean