5 September 2012
Two new studies by the Genetic Variation and Cancer Group published
Two new papers highlight aspects of the research performed by the group. One describes a new methodology for the genetic analysis of tumors and the other is a collaboration on a study that found a possible therapeutic target for a type of soft tissue sarcoma.
A new methodology for analyzing tumors has been published in PLoS ONE by the Genetic Variation and Cancer group at the IMPPC.
The method, called Microsatellite multiplex PCR analysis (MMPA), can be used to analyze the altered genomic structure in tumors and help to identify regions of the genome containing genes important for cancer development or progression.
Genetic alterations, such as copy number or copy neutral changes generate allelic imbalances (AIs), which can be identified using polymorphic markers like microsatelites. Analyzing and interpreting the somatic genetic alterations found in tumors is not an easy task, but this information needs to be integrated with other types of genetic and biological information about the tumor. Genetic analysis can be further hampered by cellular heterogeneity and the infiltration of non-altered normal cells into tumors.
The new method consists of a simple set of calculations to analyze microsatellite multiplex PCR data from control-tumor pairs and can be used to obtain accurate information about the percentage of tumor-infiltrating normal cells, the locus copy-number status and the mechanisms involved in allelic imbalances. It should be particularly useful for analyzing specific regions of the genome containing tumor suppressor genes. The method represents a simplification of the process of genetic analysis of tumors.
Aurora Kinase A as a Potential Malignant Peripheral Nerve Sheath Tumor Therapeutic Target
The Genetic Variation and Cancer Group has also participated in a study by the group led by Dr. Nancy Ratner, from the Division of Experimental Hematology and Cancer Biology of the Cincinnati Children's Hospital, just published in Clinical Cancer Research. The work aimed to use a comprehensive gene expression analysis to identify novel therapeutic targets for a type of soft tissue sarcoma, the Malignant Peripheral Nerve Sheath Tumor (MPNST), common in patients with Neurofibromatosis Type 1 disease. Aurora kinase A has been identified as a possible target for future therapies. The contribution of the IMPPC Genetic Variation and Cancer group has consisted of the genomic analysis of somatic copy number alterations of the AURKA A locus, both by SNP-array analysis and DNA qPCR, with results that were consistent with the expression analysis of the gene. Aurora kinase shRNAs and Aurora kinase inhibitors blocked MPNST cell proliferation in vitro. Additionally, an AURKA selective inhibitor, MLN8237, stabilized tumor volume and significantly increased the survival of mice with MPNST xenografts. The work shows that blocking Aurora kinases may be a viable way of treating MPNST.