Pituitary (2006) 9:165–178 DOI 10.1007/s11102-006-0262-5 Genes involved in neuroendocrine tumor biology Eva Hofsli Published online: 25 September 2006 C  Springer Science + Business Media, LLC 2006 Abstract The fascinating, but often unpredictable, biology of neuroendocrine tumors (NETs) make the management of these malignancies a real challenge. The more recent de- velopment of high-throughput genomic and proteomic tech- niques, have opened a window to an increased knowledge of the biology of NETs. This review will discuss genes thought to play a role in the context of NE tumor biology, with partic- ularly attention to those that may be potential new diagnostic and prognostic markers, as well as therapeutic targets. NETs constitute a heterogeneous group of neoplasm that may arise in virtually every topographic localization in the body, as a consequence of malignant transformation of various types of NE cells. Since NETs arising in the gastroenteropancre- atic (GEP) or bronchopulmonary system are by far the most common, this review focuses on these entities, but lines are drawn to other NETs as well. Although large-scale gene expression analysis undoubtly have raised interesting new hypothesis concerning genes thought to play a role in tumor biology, discrepancies observed between studies and various platforms used, emphasizes the need to not only standardize the way microarray data are reported, but also to introduce standards in sample taking, processing and study design. In addition, the recognition of the complexity of the human proteome, with regard to generation of multiple isoforms from one gene, has created additional challenges. However, E. Hofsli Department of Clinical and Molecular Medicine, Faculty of Medicine, Norwegian University of Science and Technology, N-7489 Trondheim, Norway e-mail: eva.hofsli@ntnu.no E. Hofsli () Oncology Unit, St. Olavs University Hospital, Olav Kyrresgt. 17, N-7006, Trondheim, Norway e-mail: eva.hofsli@stolav.no some goals have been reached already, as new knowledge has been translated into development of novel promising therapeutics. Keywords Neuroendocrine . Microarrays . Tumor biology . Gene expression . Targeting therapy . Gastroenteropancreatic (GEP) tumors . Endocrine pancreatic tumors Introduction Neuroendocrine tumors (NETs) constitute a heterogeneous group of neoplasms that may arise in virtually every topo- graphic localization in the body, as a consequence of ma- lignant transformation of various types of NE cells (Fig. 1) [cf. 1–4]. NETs arising in the gastrointestinal (GI) and bron- chopulmonary systems are by far the most common [5–7], and this review will mainly focus on genes thought to play a role in the biology of these entities, but also draw lines to other NET entities. Although the incidence of NETs is rather low, the prevalence is high, reflecting in general, a high grade of differentiation, slow growth rate, and a lower malignancy potential than many of the most common epithelial cancers. The last decade, particularly two breakthroughs have opened the window to an increased understanding of tumor biology in general. The establishment of high-throughput gene analysis microarray techniques, first described by Schena et al. in 1995 [8], and the fulfilment in 2003 of the sequencing of the human genome [9], have in the search for new diagnostic, prognostic and predictive markers, as well as novel therapeutic targets, made hypotheses-generating stud- ies possible. Furthermore, in some tumor types, gene expres- sion analysis has come up to be a valuable tool in the sub- classification of tumors, and thus may guide in the selection Springer