Dataset Information

Evaluation of 3 molecular-based assays for microsatellite instability detection in formalin-fixed tissues of patients with endometrial and colorectal cancers.

ABSTRACT: Microsatellite instability (MSI) status is routinely assessed in patients with colorectal and endometrial cancers as it contributes to Lynch syndrome initial screening, tumour prognosis and selecting patients for immunotherapy. Currently, standard reference methods recommended for MSI/dMMR (deficient MisMatch Repair) testing consist of immunohistochemistry and pentaplex PCR-based assays, however, novel molecular-based techniques are emerging. Here, we aimed to evaluate the performance of a custom capture-based NGS method and the Bio-Rad ddPCR and Idylla approaches for the determination of MSI status for theranostic purposes in 30 formalin-fixed paraffin embedded (FFPE) tissue samples from patients with endometrial (n?=?15) and colorectal (n?=?15) cancers. All samples were previously characterised using IHC and Promega MSI Analysis System and these assays set as golden standard. Overall agreement, sensitivity and specificity of our custom-built NGS panel were 93.30%, 93.75% and 92.86% respectively. Overall agreement, sensitivity and specificity were 100% with the Idylla MSI system. The Bio-Rad ddPCR MSI assay showed a 100% concordance, sensitivity and specificity. The custom capture-based NGS, Bio-Rad ddPCR and Idylla approaches represent viable and complementary options to IHC and Promega MSI Analysis System for the detection of MSI. Bio-Rad ddPCR and Idylla MSI assays accounts for easy and fast screening assays while the NGS approach offers the advantages to simultaneously detect MSI and clinically relevant genomic alterations.

SUBMITTER: Gilson P

PROVIDER: S-EPMC7532161 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Evaluation of 3 molecular-based assays for microsatellite instability detection in formalin-fixed tissues of patients with endometrial and colorectal cancers.

Gilson Pauline P Levy Julien J Rouyer Marie M Demange Jessica J Husson Marie M Bonnet Céline C Salleron Julia J Leroux Agnès A Merlin Jean-Louis JL Harlé Alexandre A

Scientific reports 20201002 1

Microsatellite instability (MSI) status is routinely assessed in patients with colorectal and endometrial cancers as it contributes to Lynch syndrome initial screening, tumour prognosis and selecting patients for immunotherapy. Currently, standard reference methods recommended for MSI/dMMR (deficient MisMatch Repair) testing consist of immunohistochemistry and pentaplex PCR-based assays, however, novel molecular-based techniques are emerging. Here, we aimed to evaluate the performance of a custo ...[more]

PMID: 33009475

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Project description:Colorectal cancer is the second leading cause of cancer death worldwide, and the incidence of this disease is expected to increase as global socioeconomic changes occur. Immune checkpoint inhibition therapy is effective in treating a minority of colorectal cancer tumors; however, microsatellite stable tumors do not respond well to this treatment. Emerging cancer immunotherapeutic strategies aim to activate a cytotoxic T cell response against tumor-specific antigens, presented exclusively at the cell surface of cancer cells. These antigens are rare and are most effectively identified with a mass spectrometry-based approach, which allows the direct sampling and sequencing of these peptides. Although the few tumor-specific antigens identified to date are derived from coding regions of the genome, recent findings indicate that a large proportion of tumor-specific antigens originate from allegedly noncoding regions. Here, we employed a novel proteogenomic approach to identify tumor antigens in a collection of colorectal cancer-derived cell lines and biopsy samples consisting of matched tumor and normal adjacent tissue. The generation of personalized cancer databases paired with mass spectrometry analyses permitted the identification of more than 30,000 unique MHC I-associated peptides. We identified 19 tumor-specific antigens in both microsatellite stable and unstable tumors, over two-thirds of which were derived from noncoding regions. Many of these peptides were derived from source genes known to be involved in colorectal cancer progression, suggesting that antigens from these genes could have therapeutic potential in a wide range of tumors. These findings could benefit the development of T cell-based vaccines, in which T cells are primed against these antigens to target and eradicate tumors. Such a vaccine could be used in tandem with existing immune checkpoint inhibition therapies, to bridge the gap in treatment efficacy across subtypes of colorectal cancer with varying prognoses. Data are available via ProteomeXchange with identifier PXD028309.

Dataset Information

Evaluation of 3 molecular-based assays for microsatellite instability detection in formalin-fixed tissues of patients with endometrial and colorectal cancers.

Publications

Evaluation of 3 molecular-based assays for microsatellite instability detection in formalin-fixed tissues of patients with endometrial and colorectal cancers.

Similar Datasets

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