Abstract

The Network Genomic Medicine: Providing Structures for Personalised Cancer Therapies

Reinhard Buettner, Director, University Hospital Cologne

Traditionally, tumors are classified by histopathological criteria, i.e., based on their specific morphological appearances. Consequently, current therapeutic decisions in oncology are strongly influenced by histology rather than underlying molecular or genomic aberrations. The increase of information on molecular changes however, enabled by the Human Genome Project and the International Cancer Genome Consortium as well as the manifold advances in molecular biology and high-throughput sequencing techniques, inaugurated the integration of genomic information into disease classification. We have therefore introduced multiplex deep sequencing of informative gene sets into routine histopathological diagnostics and molecular pathology. This comprehensive approach integrating morphological and molecular information is currently changing cancer diagnostics in five categories: (1) Somatic genomic or epigenomic alterations acquired during cancerogenesis may be used for disease classification as we show this approach adding important information to conventional morphological classifications. (2) A significant portion of solid tumors depend on oncogenic driver lesions, which provide molecular targets for prediction of effective and selective therapies. (3) Genomic alterations in signal transduction cascades and gene expression pattern may be used as prognostic parameters predicting the need and extent of adjuvant therapy. (4) In the case of multiple syn- or metachronous tumors, genomic profiling assists allocation of metastases from tumors with unknown primary (CUP) and correct staging as multiple small primary tumors and systemic metastases are reliable being discriminated. (5) Finally, mutational profiling of tumor circulating tumor DNA may facilitate monitoring the response of tumors to therapy and development of secondary resistance.