Oncomine™ Comprehensive Assay v3 vs. Oncomine™ Comprehensive Assay Plus

Abstract

The usage of next generation sequencing in combination with targeted gene panels has enforced a better understanding of tumor compositions. The identification of key genomic biomarkers underlying a disease are crucial for diagnosis, prognosis, treatment and therapeutic responses. The Oncomine™ Comprehensive Assay v3 (OCAv3) covers 161 cancer-associated genes and is routinely employed to support clinical decision making for a therapeutic course. An improved version, Oncomine™ Comprehensive Assay Plus (OCA-Plus), has been recently developed, covering 501 genes (144 overlapping with OCAv3) in addition to microsatellite instability (MSI) and tumor mutational burden (TMB) assays in one workflow. The validation of MSI and TMB was not addressed in the present study. However, the implementation of new assays must be validated and confirmed across multiple samples before it can be introduced into a clinical setting. Here, we report the comparison of DNA sequencing results from 50 ovarian cancer formalin-fixed, paraffin-embedded samples subjected to OCAv3 and OCA-Plus. A validation assessment of gene mutations identified using OCA-Plus was performed on the 144 overlapping genes and 313,769 intersecting nucleotide positions of the OCAv3 and the OCA-Plus. Our results showed a 91% concordance within variants classified as likely-pathogenic or pathogenic. Moreover, results showed that a region of PTEN is poorly covered by the OCA-Plus assay, hence, we implemented rescue filters for those variants. In conclusion, the OCA-Plus can reflect the mutational profile of genomic variants compared with OCAv3 of 144 overlapping genes, without compromising performance.

Potential Targeted Therapies in Ovarian Cancer

“…Differences in patient selection may be another explanation. In the study by Patch et al, 39% were platinum-sensitive and 61% were platinum-resistant or -refractory, while TCGA included 69% platinum-sensitive and 31% platinum-resistant patients [10,11]. In TCGA and Patch et al, platinum status was defined as resistant if the patient had progressed or recurred within 6 months after the end of the last treatment, which is consistent with our definition.…”

“…The most extensive study based on data from the TCGA database showed TP53 mutations in 88% and BRCA1/2 mutations in 23% of 316 HGSC tumors [10]. Patch et al characterized the mutational profile of 80 HGSC patients [11]. They found TP53 mutations in 99% and BRCA1/2 mutations in 26%.…”

Diagnostic Validation of a Comprehensive Targeted Panel for Broad Mutational and Biomarker Analysis in Solid Tumors

“…Moreover, analysis of the biomarkers MSI and TMB will help to select patients for immunotherapy. Other validation reports investigated a much lower number of genes, less variant types or biomarkers, or a much lower number of retro-or prospective diagnostic samples [21][22][23]. To assess the clinical value of the comprehensive TSO500 analysis compared to small panel screenings, we have set up the real-world BALLETT study (Belgian Approach of Local Laboratory Extensive Tumor Testing; https://clinicaltrials.gov/ ct2/show/NCT05058937, accessed on 5 May 2022) with the aim of introducing CGP for precision oncology and to increase treatment options for cancer patients in Belgium.…”

Cytomorphologic features of SMARCA4‐deficient non–small cell lung carcinoma and correlation with immunohistochemical and molecular features

“…All tumor specimens underwent comprehensive, targeted, next‐generation sequencing using the Oncomine assay at Yale Tumor Profiling Laboratory 28 . Briefly, the tumor percentage was visually estimated on hematoxylin‐and‐eosin–stained samples (or on immunohistochemical‐stained samples for some cases) by a molecular pathologist.…”