title: Translating tumor biology into personalized treatment planning: analytical performance characteristics of the Oncotype DX Colon Cancer Assay.
abstract: BACKGROUND
  The Oncotype DX Colon Cancer Assay is a new diagnostic test for determining the likelihood of recurrence in stage II colon cancer patients after surgical resection using fixed paraffin embedded (FPE) primary colon tumor tissue. Like the Oncotype DX Breast Cancer Assay, this is a high complexity, multi-analyte, reverse transcription (RT) polymerase chain reaction (PCR) assay that measures the expression levels of specific cancer-related genes. By capturing the biology underlying each patient's tumor, the Oncotype DX Colon Cancer Assay provides a Recurrence Score (RS) that reflects an individualized risk of disease recurrence. Here we describe its analytical performance using pre-determined performance criteria, which is a critical component of molecular diagnostic test validation.
  
  
  RESULTS
  All analytical measurements met pre-specified performance criteria. PCR amplification efficiency for all 12 assays was high, ranging from 96% to 107%, while linearity was demonstrated over an 11 log2 concentration range for all assays. Based on estimated components of variance for FPE RNA pools, analytical reproducibility and precision demonstrated low SDs for individual genes (0.16 to 0.32 CTs), gene groups (≤ 0.05 normalized/aggregate CTs) and RS (≤ 1.38 RS units).
  
  
  CONCLUSIONS
  Analytical performance characteristics shown here for both individual genes and gene groups in the Oncotype DX Colon Cancer Assay demonstrate consistent translation of specific biology of individual tumors into clinically useful diagnostic information. The results of these studies illustrate how the analytical capability of the Oncotype DX Colon Cancer Assay has enabled clinical validation of a test to determine individualized recurrence risk after colon cancer surgery.
authors.affiliation: Genomic Health, Inc., Redwood City, CA 94063, USA. klangone@genomichealth.com
authors.forename: Kim M
authors.initials: KM
authors.lastname: Clark-Langone
authors.forename: Chithra
authors.initials: C
authors.lastname: Sangli
authors.forename: Jayadevi
authors.initials: J
authors.lastname: Krishnakumar
authors.forename: Drew
authors.initials: D
authors.lastname: Watson
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D002288:Adenocarcinoma, Mucinous / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D014408:Biomarkers, Tumor / Q000235:genetics*; D017024:Chemotherapy, Adjuvant; D003082:Colectomy; D003110:Colonic Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D015972:Gene Expression Regulation, Neoplastic; D005820:Genetic Testing / Q000379:methods*; D006801:Humans; D025202:Molecular Diagnostic Techniques; D009364:Neoplasm Recurrence, Local / Q000235:genetics* / Q000517:prevention & control; D009367:Neoplasm Staging; D016612:Paraffin Embedding; D018579:Patient Selection; D057285:Precision Medicine; D011237:Predictive Value of Tests; D015203:Reproducibility of Results; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016896:Treatment Outcome
chemical_list: D014408:Biomarkers, Tumor