Notes & Commentary

New Cancer-Related Mutations Found in Breast & Colon Cancers

Reviewed by Julie R. Gralow, MD

A number of genes that are involved in the development of breast and colorectal cancers previously have been identified, but now investigators have recognized scores of gene mutations that play a role in these 2 cancer types. Although more work remains to be done, this genome research has important implications for cancer diagnosis and treatment. The report was published recently in Science (2006;314:268-274).

The group identified 122 CAN genes likely involved with breast cancer and 69 CAN genes implicated in colon cancer.

Investigators at the Ludwig Center, the Howard Hughes Medical Institute, and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, applied sophisticated gene sequencing techniques to samples from 11 breast and 11 colon tumors (chosen for study because of their substantial clinical importance worldwide) and compared more than 13,000 genes in the samples to genes from normal breast and colon samples to identify mutations. They also compared those mutations to samples from other cancers of the same type. Ultimately, the group identified 122 CAN genes likely involved with breast cancer and 69 CAN genes implicated in colon cancer—many more than they had expected. Some of the genes they discovered were already known or suspected to be associated with cancer, but most had not been previously linked to the disease. Their work could not identify every possible type of mutation; there may be more genes with different mutations that also may play a role in these cancers.

The mutations found in breast cancer are very different from those found in colon cancer, according to the research team. That might help explain why different cancers behave so differently in patients, and why even tumors of the same type vary dramatically among individuals. Their results also suggest that it takes many more mutations than previously thought to stimulate a cancer.

Individual breast cancers examined in the cancer mutation discovery screen harbored an average of 12 (range, 4-23) CAN genes, whereas the average number of CAN genes in colorectal cancers was 9 (range 3 to 18). Interestingly, the researchers pointed out, each cancer specimen of a given tumor type carried its own distinct CAN-gene mutational signature, as no cancer had more than 6 mutant CAN genes in common with any other cancer.

According to these investigators, their work represents just a “first draft” of the breast and colon cancer genomes. The techniques employed in their study were not able to analyze every single gene—about 5,000 were not included in their screening—and they were unable to identify every possible type of mutation. Thus, there may be more genes with different mutations that also play a role in these cancers.

In a press release about this research, Len Lichtenfeld, MD, deputy chief medical officer of the American Cancer Society, noted: “This report brings us one more step down the line in understanding cancer processes and toward the development of new methods for truly early diagnosis. This work will also lead the way to new approaches in determining the prognosis of individual cancers, and enable us to create personalized therapeutic ‘targeted cocktails’ for the treatment of patients with cancer.”

The techniques used by these investigators also can be applied to identify mutated genes in other cancer types.

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