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Oncology StudiesSomatic changes in the cancer cell are fundamental in the development and progression of tumors. Identifying these changes is critical for the understanding of the tumorgenesis process. In addition these changes may identify targets for drug treatment, shed light on the process of tumor progression and define markers that can predict the patient prognosis and pharmaceutical response. One example of drug development based on a genomic aberration is Gleevec that has had significant efficacy for the treatment of chronic myeloid leukemia (CML). In addition, the elucidation of somatic changes may identify markers that can predict the patient prognosis and pharmaceutical response. An example of markers predicting patient prognosis is the correlation between deletions of regions on chromosome 18 and prognosis in colon cancer. Examples of markers affecting pharmaceutical response are the Her2/neu gene amplification predicting response to Trastuzumab (Herceptin) and somatic mutations in EGFR predicting response to Gefitinib. The somatic changes that occur can be categorized into: somatic point mutations and genomic rearrangements.Detection of somatic mutations requires an accurate, scalable and sensitive method. The sensitivity is important as the analyzed tumors are often not pure and require the detection of mutations present in only a subset of the cells. ParAllele BioScience variation scanning technology (based on MRD technology) fits these parameters as it is able to scan for variations in thousands of fragments in the same tube with high accuracy. Genomic rearrangements include deletion and duplications of small or large genomic sections. The most widely used method for the detection of these changes is Comparative Genomic Hybridization (CGH). While CGH can identify deletions or duplications it fails to detect loss of heterozygosity (LOH) without a change in copy number. In addition, information of the identity of the rearranged allele is lost in CGH. ParAllele Bioscience allele quantitation technology (based on the MIP technology) is able to detect single copy changes in impure tumors. A copy number change will be detected irrespective of whether the marker is informative or not, but only informative marker will detect LOH events that are not accompanied by copy number changes. |
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