In addition to the novel discovery about regions of high-level amplification and homozygous deletions from human cancers, we have demonstrated a new method for determining DNA copy number changes by using SNP array. This method is integrated in the dCHIP software, which is highly automated and widely used in the scientific community.

Over the decades, we have learned that cancer is a genetic disease and the clonal evolution of cancer toward malignancy is due to the accumulation of genetic alterations that are advantageous to cancer cell growth when compared to normal cells. Those genetic alterations could lead to activation of oncogenes and inactivation of tumor suppressor genes.

In this study, we have shown that high-density SNP arrays is a highly efficient method for assessing copy number alterations throughout the entire genome, which provides a basis for pinpointing cancer-causing genes and identifying molecular rearrangements that correlate with clinical outcomes.

In addition, the detection of single-copy changes with SNP arrays suggests that these arrays could be used to study other genetic diseases in addition to cancers, such as Down, Prader-Willi, Angelman, and cri du chat syndromes. The SNP arrays may offer significant diagnostic potential in this area.

My group has had a long-time interest in identifying and understanding the molecular events that cause human diseases, in which we focus these efforts on human cancers and on uncovering infectious causes for diseases of unknown origin. In a previous study published in 2000, our group demonstrated that SNP arrays (Affymetrix) covering 1,494 SNP loci could accurately measure genome-wide LOH in human cancers.

In 1999 and 2000, two groups presented array-based Comparative Genomic Hybridization (CGH) methods, making it possible to scan the genome for a copy number with high resolution by hybridizing to arrayed bacterial artificial chromosome (BAC) clones. However, both methods cannot simultaneously detect LOH.

In 2003, Affymetrix released higher resolution of SNP array covering over 10,000 SNP loci. We reasoned that with this type of array, we could combine the detection of cancer copy number with cancer-specific LOH in the same experiments.

To explore this possibility, we developed methodologies that could detect DNA copy number changes, including amplification and homozygous deletions using SNP array. As we began using this method, we have already been able to find several novel altered regions in the genome of human lung cancers.