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Molecular analysis of lung adenocarcinomas from the SAFIR02-Lung cohort reveals new metastasis-associated copy-number alterations including frequent mutant-specific KRAS-allelic imbalance and identifies CDKN2A homozygous deletions as an independent biomarker of poor prognosis.
Br J Cancer
September 2025
Department of Genetics, Institut Curie, PSL Research University, Paris, France.
Background: Identifying molecular alterations specific to advanced lung adenocarcinomas could provide insights into tumour progression and dissemination mechanisms.
Method: We analysed tumour samples, either from locoregional lesions or distant metastases, from patients with advanced lung adenocarcinoma from the SAFIR02-Lung trial by targeted sequencing of 45 cancer genes and comparative genomic hybridisation array and compared them to early tumours samples from The Cancer Genome Atlas.
Results: Differences in copy-number alterations frequencies suggest the involvement in tumour progression of LAMB3, TNN/KIAA0040/TNR, KRAS, DAB2, MYC, EPHA3 and VIPR2, and in metastatic dissemination of AREG, ZNF503, PAX8, MMP13, JAM3, and MTURN.
Changes in food choices and dietary patterns during the lifestyle intervention and their association with type 2 diabetes risk in participants with high or low genetic risk for type 2 diabetes.
Eur J Nutr
September 2025
Institute of Public Health and Clinical Nutrition, University of Eastern Finland, PO Box 1627, 70211, Kuopio, Finland.
Purpose: To investigate how a group-based lifestyle intervention affects food choices and if the dietary patterns at the end of the intervention are associated with incidence type 2 diabetes (T2D). We also investigated if the possible associations between diet and T2D risk were modified by the genetic risk for T2D.
Methods: Participants in the T2D-GENE study were men with prediabetes aged 50-75 years, body mass index ≥ 25 kg/m, belonging in either low or high genetic risk score (GRS) tertile for T2D.
Loss of PTDSS1 in tumor cells improves immunogenicity and response to anti-PD-1 therapy.
Sci Adv
September 2025
Department of Genitourinary Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
(phosphatidylserine synthase 1) encodes an enzyme that facilitates production of phosphatidylserine (PS), which mediates a global immunosuppressive signal. Here, based on in vivo CRISPR screen, we identified PTDSS1 as a target to improve anti-PD-1 therapy. Depletion of in tumor cells increased expression of interferon-γ (IFN-γ)-regulated genes, including , , , and , even in the absence of IFN-γ stimulation in vitro.
View Article and Find Full Text PDFMatrix games between full siblings in Mendelian populations.
PLoS One
September 2025
HUN-REN Centre for Ecological Research, Institute of Evolution, Budapest, Hungary.
We develop a model that integrates evolutionary matrix game theory with Mendelian genetics. Within this framework, we define the genotype dynamics that describes how the frequencies of genotypes change in sexual diploid populations. We show that our formal definition of evolutionary stability for genotype distributions implies the stability of the corresponding interior equilibrium point in the genotype dynamics.
View Article and Find Full Text PDFPathway-based genetic association analysis for overdispersed count data.
J Appl Stat
February 2025
Department of Mathematics and Statistics, Wright State University, Dayton, Ohio, USA.
Overdispersion is a common phenomenon in genetic data, such as gene expression count data. In genetic association studies, it is important to investigate the association between a gene expression and a set of genetic variants from a pathway. However, existing approaches for pathway analysis are primarily designed for continuous and binary outcomes and are not applicable to overdispersed count data.
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