By sequencing, then comparing the whole genomes of tumors with those of the patient’s healthy cells in 50 women with breast cancer, researchers found more than 1700 mutations, most of which were unique to the individual. They identified 8 significantly mutated genes: PIK3CA, TP53, ATR, RUNX1, MYST3, PRSS8, ZNHIT2, and MAP3K1. Of these, PIK3CA (43%), TP53 (15.2%), and MAP3K1 (9.3%) were found to have the highest rates of incidence.
The novel gene MAP3K1 was found to be disabled in estrogen receptor–positive breast cancers. This gene controls programmed cell death, meaning that by being disabled, cells that should die continue to live. ATR and MYST3 also occurred in approximately 10% of breast cancers.
“Cancer genomes are extraordinarily complicated. This explains our difficulty in predicting outcomes and finding new treatments,” said Matthew J. Ellis, M.D., Ph.D., FRCP, of Washington University in St. Louis,during his presentation at the 102nd American Association for Cancer Research Annual Meeting. “To get through this experiment and find only three additional gene mutations at the 10% recurrence level was a bit of a shock.”
If a cancer’s genome can be sequenced before treatment and mutations that are rare in breast cancer but common in other cancers are identified, drugs may already exist to treat them. Ideally, the goal is to design treatments by sequencing the tumor genome when the cancer is first diagnosed, according to Ellis.