Molecular Technology Discriminates Between Cancer and Noncancer Patients

A new molecular technology has been developed to detect distinct genetic changes differentiating cancer patients from healthy individuals and could serve as a future cancer-predisposition test.

A DNA microarray has been designed that allows the measurement of the two million microsatellites found within the human genome using 300,000 probes and evaluation of global changes in the genome. This can determine whether pattern change alludes to a new mechanism disrupting the genome in cancer patients and may represent a new breast cancer-risk biomarker.

Scientists from the Virginia Bioinformatics Institute (VBI) at Virginia Tech (Blacksburg, VA, USA), used a custom CGH-like oligonucleotide array to measure the global microsatellite content in the genomes of 72 cancer, cancer-free, and high risk patient and cell line samples and 56 germline DNA and 16 in tumor or tumor cell line DNA. They found a unique, reproducible, and statistically significant pattern of 18 motif-specific microsatellite families out of 962 possible 1-6 mer repeats in breast cancer patient germline and tumor DNA but not in germline DNA of cancer-free volunteer controls or in breast cancer (BRCA) patients with BRCA1/2 gene mutations.

Microsatellites are short, repetitive DNA sequences that tend to vary greatly among individuals are used to uncover information related to a number of other genetic diseases such as Fragile-X or Huntington's disease. Only a small percentage of microsatellites have been linked to cancer and other diseases because there has not been an effective method available for evaluating large numbers of these sequences. This technology is enabling scientists to understand the role of these understudied parts of the human genome for the first time and may help explain the difference between the known genetic components in disease and those that have been explained by genomic studies. This tool can be used to identify and better understand genetic changes in many different types of cancer with the potential to serve as a universal cancer biomarker. It has already been instrumental in the discovery of a new biomarker in the estrogen-related receptor gamma (ERR-γ) gene, which indicates an individual's increased risk for breast cancer.

Harold Garner, PhD, a professor at VBI, said, "We have now arrived at a new biomarker, an indicator that could be used to evaluate the amount of risk that you have for developing cancer in the future. The description of the technology allows us to very quickly and efficiently and inexpensively measure these two million places using a uniquely designed microarray. It is the pattern on that microarray that provides us the information we need." The study was published online on January 14, 2011 in Genes, Chromosomes, and Cancer.

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Virginia Bioinformatics Institute