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Vince Dollard, Winship Cancer Institute, 404-778-4580,
January 24, 2001


Counting Alleles Leads to Better Prognosis of Colorectal Cancer

A study by researchers at Emory University's Winship Cancer Institute (WCI) and The Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins University identifies chromosomal imbalances as an accurate marker to predict recurrences of colorectal cancer. The study, "Counting Alleles to Predict Recurrence of Early Stage Colorectal Cancers," will be published in the January 19, 2002, issue of The Lancet.

Wei Zhou, Ph.D., of WCI, and Bert Vogelstein, Ph.D., of Johns Hopkins and Investigator, Howard Hughes Medical Institute, have developed a technique called Digital SNP (Single-Nucleotide Polymorphism), which accurately measures chromosomal imbalances by directly counting alleles in sample chromosomes. This is the first study to apply measurement of chromosomal imbalance to the prediction of which patients are likely to suffer a recurrence of colorectal cancer.

Colorectal Cancer is a common malignancy in the U.S., with an annual incidence of 135,000 cases, responsible for 55,000 deaths each year. Patients with advanced colorectal cancer typically have a poor prognosis for recovery. Patients with early stage colorectal cancer typically have a good prognosis, however, 10 to 30 percent of these patients develop recurrences and die from the disease. The ability to predict which of these patients might develop a recurrence would greatly benefit the patient and physician in planning for future treatment.

Previous studies have shown that when regions of certain chromosomes are lost, an imbalance results. If the lost region of the chromosome contains a tumor suppressor gene, those cells may acquire a competitive growth advantage and play an important role in the recurrence of colorectal tumors.

Accurately measuring chromosomal imbalances is extremely difficult. Dr. Zhou, Dr. Vogelstein and their team developed the Digital SNP, in which each allele in the chromosomal sample is counted, one by one, providing an unprecedented degree of accuracy to the analysis.

The study focused on two specific chromosomes (8 and 18) in which the inactivation of tumor suppressor genes indicates an important role in subsequent tumor progression. Researchers studied 180 colorectal cancer patients from four different hospitals in the U.S. and Europe over the course of five years. Using Digital SNP, a strong connection between specific chromosomal imbalances and disease recurrence emerged, providing valuable information for the prognosis and treatment of this cancer.

In addition, Digital SNP has enabled researchers to reach more definitive conclusions than previously possible. For example, microdissection is essential to obtain tumor cells, however, the amount of usable DNA recovered from microdissected cells is limited. Sampling errors based on analysis of only a few DNA molecules could lead to erroneous conclusions. This is the first study to count the number of alleles actually analyzed in each sample, which eliminates possible errors based on limited data.

Dr. Zhou and Dr. Vogelstein believe the approaches and results of allele imbalance in colorectal cancer may be applicable to other cancers. Previous studies have shown evidence of allele imbalance in at least nine different chromosomes with some relation to colorectal cancer development. It is possible then, that allele imbalance within chromosomes in general indicates greater chances of metastasis, possibly due to increased instability. If this is true, then using Digital SNP to study the allele imbalance of any chromosome that is lost during tumor progression should provide useful prognostic information.

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