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Baselga Carretero, I.

Publications and source records attributed to Baselga Carretero, I..

2 recordsLinked to original sources
bioRxiv2020

Optimizing nucleic acid extraction and transcriptome evaluation from low-input, fixed clinical samples

Tumor biopsies are commonly formalin-fixed and paraffin-embedded (FFPE) for long-term and efficient storage. However, FFPE preservation can greatly compromise the quality of samples, the extraction of nucleic acids, and feasibility of downstream studies, including RNA sequencing. These challenges are especially evident in the studies of clinical trial samples, where the sizes of biopsies often limit the amount of material available for study. Here, we evaluate two nucleic acid extraction kits (Covaris truXTRAC FFPE tNA Plus, QIAGEN miRNeasy FFPE) and three hybridized-capture-based RNA sequencing library preparations (Agilent SureSelect XT RNA Direct, Agilent SureSelect XT HS, and Illumina TruSeq RNA Exome) to evaluate the impact of these sample processing steps on transcriptome evaluation in a melanoma biopsy procured in a clinical setting and preserved by FFPE. While there exist many options for extraction and library preparation that are appropriate for RNA sequencing from FFPE samples, we observed that combinations of experimental approaches may have subtle impacts on downstream analysis, including gene expression quantification and fusion detection.

genomics↗
bioRxiv2020

Autoantibody landscape of advanced prostate cancer

Although the importance of T-cell immune responses is well appreciated in cancer, autoantibody responses are less well-characterized. Nevertheless, autoantibody responses are of great interest, as they may be concordant with T-cell responses to cancer antigens or predictive of response to cancer immunotherapies. We performed serum epitope repertoire analysis (SERA) on a total of 1,229 serum samples obtained from a cohort of 72 men with metastatic castration-resistant prostate cancer (mCRPC) and 1,157 healthy control patients to characterize the autoantibody landscape of mCRPC. Using whole-genome sequencing results from paired solid-tumor metastasis biopsies and germline specimens, we identified tumor-specific epitopes in 29 mutant and 11 non-mutant proteins. Autoantibody enrichments for the top candidate autoantigen (NY-ESO-1) were validated using ELISA performed on the prostate cancer cohort and an independent cohort of 106 patients with melanoma. Our study recovers antigens of known importance and identifies novel tumor-specific epitopes of translational interest in advanced prostate cancer. Statement of significanceAutoantibodies have been shown to inform treatment response and candidate drug targets in various cancers. We present the first large-scale profiling of autoantibodies in advanced prostate cancer, utilizing a new next-generation sequencing-based approach to antibody profiling to reveal novel cancer-specific antigens and epitopes. Disclosure of Potential Conflicts of InterestJJA reports receiving consulting income from Janssen Biotech and Merck and honoraria from Astellas for speakers fees. MR reports receiving commercial research support from Novartis, Johnson & Johnson, Merck, Astellas, and Medivation, and is a consultant/advisory board member for Constellation Pharmaceuticals, Amgen, Ambrx, Johnson & Johnson, and Bayer. A.R. has received honoraria from consulting with Amgen, Bristol-Myers Squibb, Chugai, Dynavax, Genentech, Merck, Nektar, Novartis, Roche and Sanofi, is or has been a member of the scientific advisory board and holds stock in Advaxis, Arcus Biosciences, Bioncotech Therapeutics, Compugen, CytomX, Five Prime, RAPT, ImaginAb, Isoplexis, Kite-Gilead, Lutris Pharma, Merus, PACT Pharma, Rgenix and Tango Therapeutics. FYF serves on the advisory board for Dendreon, EMD Serono, Janssen Oncology, Ferring, Sanofi, Blue Earth Diagnostics, Celgene, consults for Bayer, Medivation/Astellas, Genetech, and Nutcracker Therapeutics, has honoraria from Clovis Oncology, and is a founder and has an ownership stake in PFS Genomics. SGZ and FYF have patent applications with Decipher Biosciences. SGZ and FYF have a patent application licensed to PFS Genomics. SGZ and FYF have patent applications with Celgene. WAH, RW, KK, PSD, and JCS have ownership of stocks or shares at Serimmune, paid employment at Serimmune, board membership at Serimmune, and patent applications on behalf of Serimmune.

cancer biology↗