Biomedical subjects

Christophe Redon

Publications and source records attributed to Christophe Redon.

3 recordsLinked to original sources

PubMed2026

SCLC TumorMiner: A genomics platform for small cell lung cancer precision oncology.

Small cell lung cancer (SCLC) is among the most aggressive malignancies. Unlike many other cancers, it is not represented in The Cancer Genome Atlas, and available datasets are fragmented across institutions, disease stages, and treatment settings. RNA sequencing provides a powerful and cost-effective approach, but the high dimensionality of transcriptomic data and the heterogeneity of patient cohorts pose significant challenges. To address such challenges, we developed SCLC TumorMiner (https://discover.nci.nih.gov/SclcTumorMinerCDB/), which includes 50 tumor samples from relapsed patients at the National Cancer Institute (NCI) and 154 samples from untreated patients at the University of Cologne and Tongji University. SCLC TumorMiner enables molecular classification, genomic pathway analyses, risk stratification, identification of predictive cell-surface biomarkers such as DLL3 or TROP2, and drug-response biomarkers such as SLFN11. SCLC TumorMiner illustrates profound differences between untreated and relapsed patient samples. Additionally, "MyPatient", one of SCLC TumorMiner's modules, is presented as a medical assistant application prototype.

SCLC↗

PubMed2025

Lamin A/C loss promotes R-loop-mediated genomic instability and poor survival in small-cell lung cancer.

Lamin A/C (LMNA), a key component of the nuclear envelope, is essential for maintaining nuclear integrity and genome organization [W. Xie et al., Curr. Biol. 26, 2651-2658 (2016)]. While LMNA dysregulation has been implicated in genomic instability across cancer and aging, the underlying mechanisms remain poorly understood [S. Graziano et al., Nucleus 9, 258-275 (2018)]. Here, we define a mechanistic role for LMNA in preserving genome stability in small-cell lung cancer (SCLC), a malignancy marked by extreme genomic instability [N. Takahashi et al., Cancer Res. Commun. 2, 503-517 (2022)]. LMNA depletion promotes R-loop accumulation, transcription-replication conflicts, replication stress, DNA breaks, and micronuclei formation. Mechanistically, LMNA deficiency disrupts nuclear pore complex organization, specifically reducing phenylalanine-glycine (FG)-nucleoporin incorporation, resulting in impaired RNA export and nuclear retention of RNA. LMNA expression is repressed by EZH2 and reexpressed during SCLC differentiation from neuroendocrine (NE) to non-NE states, and low LMNA levels correlate with poor clinical outcomes. These findings establish LMNA as a key regulator of nuclear transport and genome integrity, linking nuclear architecture to SCLC progression and therapeutic vulnerability.

Lamin Type A↗

PubMed2025

Lamin A/C Deficiency Drives Genomic Instability and Poor Survival in Small-Cell Lung Cancer through Increased R-loop Accumulation.

Lamin A/C (LMNA), a key component of the nuclear envelope, is essential for maintaining nuclear integrity and genome organization [1]. While LMNA dysregulation has been implicated in genomic instability across cancer and aging, the underlying mechanisms remain poorly understood [2]. Here, we investigate LMNA's role in small-cell lung cancer (SCLC), a highly aggressive malignancy characterized by extreme genomic instability [3, 4]. We demonstrate that LMNA depletion promotes R-loop accumulation, transcription-replication conflicts, replication stress, DNA breaks, and micronuclei formation. Mechanistically, LMNA loss disrupts nuclear pore complex distribution, reducing phenylalanine-glycine (FG)-nucleoporin incorporation and impairing RNA export efficiency. Furthermore, we show that LMNA expression is epigenetically repressed by EZH2 during SCLC differentiation from neuroendocrine (NE) to non-NE states. Clinically, low LMNA levels correlate with significantly worse survival in SCLC patients. These findings uncover a novel role for LMNA in safeguarding genome integrity and shaping tumor heterogeneity, with broad implications for cancer and aging.

Biological Sciences↗