Researchers at Washington University School of Medicine in St. Louis have identified mutated genes directly involved in 12 cancers. Li Ding, PhD, of The Genome Institute at Washington University analyzed 3,281 malignant tumors found the breast, uterus, head and neck, colon and rectum, bladder, kidney, ovary, lung, brain and blood and published her research in the journal of Nature and her findings show a correlation between different cancer types.
A gene mutation occurring in 25% of leukemia cases was also found in tumors of the breast, rectum, head and neck, kidney, lung, ovary and uterus. Dr. Ling’s research is one of the few studies to examine similarities across many different types of cancers.
“This is just the beginning,” said senior author Li Ding, PhD, of The Genome Institute at Washington University. “Many oncologists and scientists have wondered whether it’s possible to come up with a complete list of cancer genes responsible for all human cancers. I think we’re getting closer to that.”
The genetic analysis did not only find correlations among different cancers but also identified a number of mutations exclusive to particular cancer types that drive cancer, with two to six mutations causing the malignancy. “While cells in the body continually accumulate new mutations over the years, it only takes a few mutations in key driver genes to transform a healthy cell into a cancer cell,” noted Ding.
Specific genes were also implicated in cancer survival rate. TP53, an already well-known cancer gene, occurred most commonly across the different tumor types. It was found in 42 percent of samples and routinely was associated with a poor prognosis, particularly in kidney cancer, head and neck cancer and acute myeloid leukemia.
Another gene, BAP1, also was linked with an unfavorable prognosis, especially in patients with kidney and uterine cancer.
Mutations in the breast cancer gene BRCA2 were associated with improved survival in ovarian cancer, while errors in IDH1 were linked to an improved prognosis in gliobastoma, a particularly aggressive brain tumor, and in other cancer types.
“Because we now know, for example, that genes mutated in leukemia also can be altered in breast cancer and that genetic errors in lung cancer also can show up in colon and rectal cancer, we think one inclusive diagnostic test that includes all cancer genes would be ideal,” Ding said. “This would provide a more complete picture of what’s going on in a tumor, and that information could be used to make decisions about treatment.”
Kandoth C, McLellan MD, Vandin F, Ye K, Niu B, Lu C, Xie M, Zhang Q, McMichael JF, Wyczalkowski MA, Leiserson MDM, Miller CA, Welch JS, Walter MJ, Wendl MC, Ley TJ, Wilson RK, Raphael BJ and Ding L. Mutational landscape and significance across 12 major cancer types. Nature online Oct. 17, 2013.