Tissue of Origin Test Kit-FFPE

The Cancer Genetics Tissue of Origin Test Kit-FFPE is an in vitro diagnostic that compares RNA expression patterns from a patient's FFPE tumor to a database of fifteen tumor types using microarray technology and a similarity score algorithm. Its purpose is to assist physicians by providing additional information on tumor characteristics, with stated limitations regarding definitive diagnosis of origin, subclassification, or prognostic predictions.

The Cancer Genetics Tissue of Origin Test Kit-FFPE is an in vitro diagnostic tool designed to measure the similarity between RNA expression patterns in a patient's formalin-fixed, paraffin-embedded (FFPE) tumor and RNA expression patterns from a database of fifteen specific tumor types. These database tumor types include poorly differentiated, undifferentiated, and metastatic cases diagnosed by standard clinical and pathological practices. The methodology involves using a reagent kit, a microchip (Pathchip® with 2000 gene expression probes), and software to compare these expression patterns. The test requires external equipment, including an Affymetrix GeneChip Fluidics Station, GeneChip Scanner, and a workstation with GeneChip Operating System. It is intended to be used by a qualified physician in conjunction with other clinical and diagnostic information. This document details modifications to the test, specifically a change in the RNA amplification method and reagents from the RampUp RNA amplification Kit to the GeneChip™ 3' IVT Pico Kit, and an update to the microarray processing software from Genechip™ System 3000 Dx to Genechip™ System 3000 Dx v.2. Non-clinical validation studies showed a 90.8% concordance (133 out of 142 specimens) for the reagent change and 100% concordance (20 out of 20 specimens) for the software update when results were compared to the previous methods. The test has limitations: it is not intended to establish the origin of tumors that cannot be diagnosed by current practices (e.g., cancer of unknown primary), nor to subclassify tumors, predict disease course, survival, treatment efficacy, or distinguish primary from metastatic tumors. Furthermore, results cannot distinguish tumor types in the database from those not in the database if they exhibit similar RNA expression patterns.

AI Regulatory Concerns

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• Q1. What are the specific 2000 gene expression probes employed by the Pathchip® microarray, and how were they selected for differentiating the 15 tumor types?; How does the 'similarity score algorithm' quantitatively determine the degree of similarity between a patient's tumor RNA expression and the database profiles?; What were the characteristics of the 9 discordant cases in the reagent comparison study (133/142 concordance), and could these discrepancies highlight specific sensitivities or limitations of the new GeneChip™ 3' IVT Pico Kit?; Given the limitation that tumor types not in the database may show similar RNA patterns, what is the potential rate of misinterpretation or inconclusive results when applied to a diverse clinical population beyond the validation set?; What were the pre-established acceptance criteria for the reagent modification study that deemed the 90.8% concordance (133/142) as successful validation?