LACE-Bio-II: Identification, validation and implementation of prognostic and/or p

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DESCRIPTION (provided by applicant): Investigators from the four pivotal adjuvant NSCLC trials (IALT, CALGB 9633, JBR.10, ANITA) formed the Lung Adjuvant Cisplatin Evaluation (LACE)-Bio-I consortium to conduct cross-validation/pooled meta-analyses of biomarkers that each group had identified on collected formalin fixed tumor (FFPE) to confirm their robustness/utility in a larger dataset. LACE-Bio-I had a focus predominantly on immunohistochemical methods (IHC) and single gene analyses. JBR.10 also collected fresh frozen tumor (FFT) and normal lung in a subset of patients and has identified an mRNA expression signature that is strongly prognostic and may be predictive of benefit from cisplatin/vinorelbine ACT. With the ongoing cancer genome sequencing efforts in lung cancer and the reporting of identification of novel genetic aberrations that represent crucial "oncogenic drivers" in NSCLC, we also urgently need a more adaptive strategy to explore the value of these new markers as prognostic and predictive markers in early stage patients. LACE-Bio-II has a new strategic direction. We will explore novel markers that are nucleic acid based, including gene copy number changes (amplifications and deletions), somatic gene mutations, and RNA-based markers that may involve multi-gene mRNA signatures. Using LACE-Bio FFPE tumor samples, we plan to validate the JBR.10 15-gene prognostic and predictive mRNA signature, evaluate the prognostic and predictive values of known potential oncogenic mutations, and explore the prognostic and predictive values of gene copy variations. We will also identify and evaluate the prognostic and predictive value of novel genomic aberrations discovered by Next Generation Sequencing on snap-frozen JBR.10 samples. New high performance and sensitive technologies for assaying and quantifying genomic aberrations using nucleic acid materials derived from FFPE samples have been developed and been introduced into Clinical Laboratory Improvement Amendments (CLIA)-approved laboratories. Should our strategy be successful, identified and validated markers can be rapidly introduced into clinical practice.