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Novel gene predicts local recurrence in early-onset breast cancer
Date:5/5/2009

recurrence up to 12 years after surgery," Killary said. Of the 123 early-onset patients, 72 percent had no lymph node involvement at diagnosis.

Low expression associated with triple-negative breast cancer

While the researchers found that loss of DEAR1 expression correlated significantly with local recurrence, it did not correlate with overall survival in this young cohort.

However, lack of DEAR1 expression was associated with triple-negative breast cancer, which indicates poor prognosis because it lacks estrogen or progesterone receptors and does not express HER2, three targets for therapy. Lack of DEAR1 expression also was associated with a strong family history of breast cancer.

The team discovered the gene in a region of the human genome that has been implicated in other epithelial tumors, including colon and pancreatic cancers, and that the researchers suspected might harbor an important tumor suppressor gene. Finding that DEAR1 was mutated in breast cancer suggested that it could play a role in the initiation and progression of the disease.

The researchers found evidence that DEAR1 plays a critical regulatory role in acinar morphogenesis, or the orderly development and differentiation of the terminal ductal lobular units (TDLU) in the breast. TDLUs are structures present at the ends of a branching network of ducts in the normal mammary gland which also are thought to be the site of origin of many breast cancers. Mutations in DEAR1 lead to cellular disorganization, lack of cell differentiation, and loss of normal structure in breast tissue - all hallmarks of a transition to malignancy.

Mutated or deleted DEAR1 causes structural dysfunction

The researchers tested their theories in an experimental model using three-dimensional basement membrane culture systems designed to reproduce the tissue architecture of the mammary gland.

The first experiment tested whether placing a n
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Contact: Scott Merville
smerville@mdanderson.org
713-792-0661
University of Texas M. D. Anderson Cancer Center
Source:Eurekalert  

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