Genome Wide DNA Copy Number Analysis of Serous Type Ovarian Carcinomas Identifies Genetic Markers Predictive of Clinical Outcome

Ovarian cancer is the fifth leading cause of cancer death in women. Ovarian cancers display a high degree of complex genetic alterations involving many oncogenes and tumor suppressor genes. Analysis of the association between genetic alterations and clinical endpoints such as survival will lead to improved patient management via genetic stratification of patients into clinically relevant subgroups. In this study, we aim to define subgroups of high-grade serous ovarian carcinomas that differ with respect to prognosis and overall survival. Genome-wide DNA copy number alterations (CNAs) were measured in 72 clinically annotated, high-grade serous tumors using high-resolution oligonucleotide arrays. Two clinically annotated, independent cohorts were used for validation. Unsupervised hierarchical clustering of copy number data derived from the 72 patient cohort resulted in two clusters with significant difference in progression free survival (PFS) and a marginal difference in overall survival (OS). GISTIC analysis of the two clusters identified altered regions unique to each cluster. Supervised clustering of two independent large cohorts of high-grade serous tumors using the classification scheme derived from the two initial clusters validated our results and identified 8 genomic regions that are distinctly different among the subgroups. These 8 regions map to 8p21.3, 8p23.2, 12p12.1, 17p11.2, 17p12, 19q12, 20q11.21 and 20q13.12; and harbor potential oncogenes and tumor suppressor genes that are likely to be involved in the pathogenesis of ovarian carcinoma. We have identified a set of genetic alterations that could be used for stratification of high-grade serous tumors into clinically relevant treatment subgroups

Response evaluation and follow-up by imaging in brain tumours

Brain tumours, either primary or secondary, are frequent. Primary brain tumours include mainly glioma, lymphoma and meningioma. Secondary tumours, i.e. brain metastases, are a frequent event during the disease course of patients with cancer. The evaluation of response to treatment is often difficult with structural imaging due to the interference of treatment effects. In this chapter, the role of advanced imaging for the differential diagnosis between pseudoprogression, radiation necrosis and tumour recurrence is described with perfusion and diffusion MR imaging, MR spectroscopy and PET imaging with amino acid analogues, fluorodeoxyglucose and other tracers. Furthermore, the commonly used response criteria for various brain tumours are described. For glioma, those set out by the response assessment in neuro-oncology (RANO) group are recommended. For brain metastases the RANO-brain metastases (RANO-BM) and RECIST criteria are commonly used. While conventional T1w post-contrast imaging is the mainstay imaging modality for basic response assessment, multimodal imaging is commonly necessary to evaluate the response to treatment of primary and secondary brain tumours