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| From OncoLog,
April 2006, Vol. 51, No. 4 |
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Breaks in “Backward” DNA Associated with Leukemia
When otherwise normal DNA adopts an unusual shape called Z-DNA, it can lead to the kind of genetic instability associated with cancers such as leukemia and lymphoma, according to a study by researchers at The University of Texas M. D. Anderson Cancer Center.
The study, presented in the February 21 edition of the Proceedings of the National Academy of Sciences, demonstrates for the first time that the odd shape can cause DNA breaks in mammalian cells. Interestingly, sequences prone to forming Z-DNA are often found in genetic “hot spots,” areas of DNA prone to the genetic rearrangements associated with cancer. About 90% of patients with Burkitt’s lymphoma, for example, have DNA breaks that map to regions with the potential to form these odd DNA structures.
Imagine untwisting the DNA ladder and then winding it up the other way. The resulting “Z-DNA” would be a twisted mess with segments jutting out left and right and with the all-important base pairs that hold the DNA code zigzagging like a jagged zipper. It just doesn’t look right, and it doesn’t act right, either, according to Karen Vasquez, Ph.D., lead author of the study and assistant professor of carcinogenesis at M. D. Anderson Cancer Center’s Science Park Research Division. This awkward shape can cause the DNA molecule to break completely apart.
“Our study shows that DNA itself can act as a mutagen, resulting in genetic instability,” said Dr. Vasquez. “The discovery opens up a new field of inquiry into the role of DNA shape in genomic instability and cancer.”
Preventing Cancers in Women with Lynch Syndrome
Women diagnosed with Lynch syndrome, a condition often associated with colon cancer, also are at high risk for endometrial and ovarian cancers—both of which can be eliminated by having a prophylactic hysterectomy and oophorectomy, according to a study published by researchers from M. D. Anderson in the January 19 issue of the New England Journal of Medicine.
Lynch syndrome is an inherited disorder in which affected individuals have a much higher-than-normal chance of developing colon cancer and/or certain other types of cancer, usually before the age of 60.
“The key reason that we embarked on this study was that women with Lynch syndrome often don’t realize that they are at an extremely high risk for two gynecological cancers,” said Karen Lu, M.D., associate professor in M. D. Anderson’s Department of Gynecologic Oncology.
Women with Lynch syndrome have a 40% to 60% lifetime risk of developing endometrial cancer and a 10% to 12% lifetime risk of ovarian cancer, said Dr. Lu. In the general population, the risk of endometrial cancer is about 3%, and the risk of ovarian cancer is 1% to 2%.
“This study is an important reminder to physicians to pay attention to a woman’s family history of colon, endometrial, and ovarian cancers, with genetic counseling becoming of utmost importance. If women with Lynch syndrome are identified, there needs to be coordinated care between the gastrointestinal and obstetrics and gynecologic medical disciplines,” Dr. Lu said.
Erratum
In the March In Brief about Dr. Qingyi Wei’s research on skin cancer, we incorrectly called basal cell carcinoma and squamous cell carcinoma “nonmalignant” instead of “nonmelanoma.” These tumors can and do spread locally, regionally, and diffusely, and there are several thousand deaths each year in the U.S. from these two skin cancers. We regret the error.—Eds.
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