Clinical Utility of SNP Microarrays in Adult Brain Tumors: Molecular Insight into Tumor Heterogeneity and Progression

Abstract

s 215 cases. In at least two cases, array testing provided information that would have been of major prognostic importance if available at the time of diagnosis. This data illustrates that whole genome arrays represent a suitable tool for the detection of prognostic genomic aberrations from FFPE material in MS, in a clinical diagnostic setting. High Resolution SNP Microarray Analysis is Useful for Diagnosis and Prognosis of Renal Epithelial Neoplasms Daynna J. Wolff , James S. Rosoff , Heidi H. Hamilton , M. Timothy Smith a Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA; Department of Urology, Medical University of South Carolina, Charleston, SC, USA Renal epithelial neoplasms (REN) are common in adults with approximately 54,000 newly diagnosed cases each year and over 13,000 deaths. Diagnosis and classification of REN can be difficult based uponhistologic and clinical information, however, the prediction of which patients will have recurrent disease and/or disease progression is even more challenging. Single nucleotide polymorphism (SNP) microarray analysis has been shown to be useful in stratifying the four major classes of REN for diagnosis into clear cell renal cell carcinoma (RCC), papillary RCC, chromophobe RCC and oncocytoma. The aim of this study was to determine if microarray analysis could also be useful for identifying markers associated with RCC cases with a high risk for recurrence and/or metastasis. High resolution SNP microarray (Illumina Omni-1) analysis was performed on 41 fresh renal tumors. An overall concordance rate of 83%was observed between the histologic and genetic classification confirming the utility of SNP analysis in the subclassification of REN. In addition, several genetic markers, including loss of 4q, 9/9p, 14 and 18, were associatedwith high-risk histologic features and with clinical data showing evidence of disease following nephrectomy and/or progression/metastasis. Amplificationsandchromothripsiswereonlyseen inRCCwith highrisk features. These studies show that SNP microarray genomic analysis can provide important prognostic information and could be useful to guide treatment for patients with RCC. Clinical Utility of SNP Microarrays in Adult Brain Tumors: Molecular Insight into Tumor Heterogeneity and Progression Iya Znoyko, Cynthia Welsh, Daynna Wolff Department of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston, SC, USA Each year in the US, there are approximately 23,000 newly diagnosed brain tumors and 14,000 related deaths. Somatic genetic abnormalities have been associated with histological subtype and grade of common adult brain tumors, gliomas and meningiomas. High resolution SNP microarray analysis could provide valuable information on genetic aberrations associated with brain tumors, assisting in stratification for prognosis and treatment. DNA from fresh brain tissue of 2 patients with high grade glioblastoma (WHO IV), 2 patients with low grade astrocytoma (WHO II and I), and a patient with meningioma (WHO I) was analyzed by Illumina SNP microarray; for two of above patients, FFPE samples were analyzed in parallel. Results were compared to histopathological studies. In all cases SNP microarray revealed results that correlated with histopathological diagnosis and for 4/5 cases, additional clinically relevant information was provided. Microarray results from two glioblastoma cases and one case of astrocytoma allowed for subtyping of the disease. The genetic aberrations observed in two cases with low grade tumors [meningioma (WHO I), astrocytoma (WHO II)] suggested potential progression to higher grade. Comparative analysis of both cases with fresh and fixed tissue samples from tumor enriched areas (one astrocytoma and one high grade glioma) revealed genetic heterogeneity. Our data demonstrate the feasibility of using high resolution SNP analysis for studies of adult brain tumors both on fresh and fixed tissue. Genetic profiling facilitates detailed stratification of tumors into subtypes and allows for the identification of genetic markers that may be associated with tumor progression. The observed tumor heterogeneity in the astrocytoma and glioma cases corroborates previous FISH studies and suggests a multiclonal mechanism of tumor progression in low and high grade gliomas rather than gradual clonal evolution. This, together with chromothripsis, could reflect an aggressive character of astrocytomas and gliomas.