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In Blood Cancer Discovery, Thibaud and colleagues report the incidence of pathogenic germline variants (PGV) in patients with multiple myeloma and that these PGVs are associated with DNA repair pathway genes, including BRCA1 and BRCA2. They find an association of patients with PGVs and previous family or personal history of cancer, and that these patients are diagnosed slightly earlier than those without PGVs. Patients with PGVs had a longer progression-free survival than those without PGVs when they received high-dose melphalan and autologous stem cell transplant, providing a therapeutic rationale for diagnostic germline testing in myeloma. See related article by Thibaud et al., p. 428.
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http://dx.doi.org/10.1158/2643-3230.BCD-24-0226 | DOI Listing |
Cancer Immunol Immunother
September 2025
Department of Medical Oncology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands.
Whole blood (WB) transcriptomics offers a minimal-invasive method to assess patients' immune system. This study aimed to identify transcriptional patterns in WB associated with clinical outcomes in patients treated with immune checkpoint inhibitors (ICIs). We performed RNA-sequencing on pre-treatment WB samples from 145 patients with advanced cancer.
View Article and Find Full Text PDFCell Genom
September 2025
Gladstone-UCSF Institute of Genomic Immunology, San Francisco, CA, USA; Department of Epidemiology and Biostatistics, University of California, San Francisco, San Francisco, CA, USA; Division of Rheumatology, Department of Medicine, University of California, San Francisco, San Francisco, CA, USA; In
Missense variants can have pleiotropic effects on protein function, and predicting these effects can be difficult. We performed near-saturation deep mutational scanning of P2RY8, a G protein-coupled receptor that promotes germinal center B cell confinement. We assayed the effect of each variant on surface expression, migration, and proliferation.
View Article and Find Full Text PDFESMO Open
September 2025
Saint Antoine Hospital, Assistance Publique Hôpitaux de Paris (APHP), Sorbonne Université, Paris, France; Unité Mixte de Recherche Scientifique 938, SIRIC CURAMUS, Paris, France.
Background: Immune checkpoint inhibitors (ICIs) represent a paradigm shift and a therapeutic revolution in the management of mismatch repair-deficient/microsatellite instability-high (dMMR/MSI-H) colorectal cancer (CRC), and therefore for patients with Lynch syndrome (LS). The risk of developing metachronous cancers and colorectal polyps in a population of LS patients treated with ICI(s) is not well understood.
Materials And Methods: In a single-center cohort study, we retrospectively reviewed 93 LS patients from the prospective 'ImmunoMSI' cohort, who were diagnosed with dMMR/MSI-H gastrointestinal cancer and were treated with ICIs for index metastatic gastrointestinal cancer between February 2015 and April 2024.
J Clin Oncol
September 2025
Sidney Kimmel Comprehensive Cancer Center Johns Hopkins University School of Medicine, Baltimore, MD.
Purpose: To assess modified folinic acid/leucovorin, fluorouracil, irinotecan, oxaliplatin (FOLFIRINOX; mFFX) versus gemcitabine/nab-paclitaxel (GnP) in de novo metastatic pancreatic ductal adenocarcinoma (PDAC) and explore predictive biomarkers.
Patients And Methods: Patients were randomly assigned 1:1 to mFFX or GnP with exclusion of germline pathogenic variants in or . The primary end point was progression-free survival (PFS) between arms with 0.
JCO Precis Oncol
September 2025
Cell Biology and Biotherapy Unit, Istituto Nazionale Tumori IRCCS Fondazione G. Pascale, Napoli, Italy.
Purpose: Tumor comprehensive genomic profiling (CGP) may detect potential germline pathogenic/likely pathogenic (P/LP) alterations as secondary findings. We analyzed the frequency of potentially germline variants and large rearrangements (LRs) in the RATIONAL study, an Italian multicenter, observational clinical trial that collects next-generation sequencing-based tumor profiling data, and evaluated how these findings were managed by the enrolling centers.
Patients And Methods: Patients prospectively enrolled in the pathway-B of the RATIONAL study and undergoing CGP with the FoundationOne CDx assays were included in the analysis.