title: Gene expression profiling in multiple myeloma--reporting of entities, risk, and targets in clinical routine.
abstract: OBJECTIVE
  Multiple myeloma is an incurable malignant plasma cell disease characterized by survival ranging from several months to more than 15 years. Assessment of risk and underlying molecular heterogeneity can be excellently done by gene expression profiling (GEP), but its way into clinical routine is hampered by the lack of an appropriate reporting tool and the integration with other prognostic factors into a single "meta" risk stratification.
  
  
  METHODS
  The GEP-report (GEP-R) was built as an open-source software developed in R for gene expression reporting in clinical practice using Affymetrix microarrays. GEP-R processes new samples by applying a documentation-by-value strategy to the raw data to be able to assign thresholds and grouping algorithms defined on a reference cohort of 262 patients with multiple myeloma. Furthermore, we integrated expression-based and conventional prognostic factors within one risk stratification (HM-metascore).
  
  
  RESULTS
  The GEP-R comprises (i) quality control, (ii) sample identity control, (iii) biologic classification, (iv) risk stratification, and (v) assessment of target genes. The resulting HM-metascore is defined as the sum over the weighted factors gene expression-based risk-assessment (UAMS-, IFM-score), proliferation, International Staging System (ISS) stage, t(4;14), and expression of prognostic target genes (AURKA, IGF1R) for which clinical grade inhibitors exist. The HM-score delineates three significantly different groups of 13.1%, 72.1%, and 14.7% of patients with a 6-year survival rate of 89.3%, 60.6%, and 18.6%, respectively.
  
  
  CONCLUSIONS
  GEP reporting allows prospective assessment of risk and target gene expression and integration of current prognostic factors in clinical routine, being customizable about novel parameters or other cancer entities.
authors: Medizinische Klinik V, Universitätsklinikum Heidelberg, Germany.
authors: Tobias
authors: T
authors: Meissner
authors: Anja
authors: A
authors: Seckinger
authors: Thierry
authors: T
authors: Rème
authors: Thomas
authors: T
authors: Hielscher
authors: Thomas
authors: T
authors: Möhler
authors: Kai
authors: K
authors: Neben
authors: Hartmut
authors: H
authors: Goldschmidt
authors: Bernard
authors: B
authors: Klein
authors: Dirk
authors: D
authors: Hose
mesh_terms: D000465:Algorithms; D002869:Chromosome Aberrations; D003627:Data Interpretation, Statistical; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D046228:Microarray Analysis; D009101:Multiple Myeloma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D012984:Software