Biology subjects

Teleanu, M.-V.

Publications and source records attributed to Teleanu, M.-V..

3 recordsLinked to original sources

bioRxiv2026

TOPAS: phosphoproteome data analysis and decision support platform for molecular tumor boards

The molecular tumor board (MTB) is central to precision oncology, providing personalized treatment recommendations based on molecular profiles of patient tumors. Genomics is instrumental for MTBs but often fails to identify clinically actionable targets, a gap that phosphoproteomics can fill. We present the tumor proteome activity status (TOPAS) platform, an end-to-end analysis pipeline that converts terabytes of phosphoproteomic data into patient-specific reports for MTB discussions, focusing on clinically relevant signaling linked to oncogenic mechanisms and therapeutic targets. Designed to scale with growing cohorts, the platform integrates data from 1,998 tumor samples to support patient- and cohort-level hypothesis generation. A web portal handles quality control, calculates TOPAS scores, identifies tumor antigens and immune checkpoints, and offers interactive analyses of differential protein abundance and outlier detection. The TOPAS platform is open source, addresses a critical unmet need and facilitates broader adoption of phosphoproteomics in precision oncology in the future.

bioinformatics↗

bioRxiv2026

Prospective pan-cancer phosphoproteomics at clinical scale extends therapeutic options in precision oncology

Genomics-guided precision oncology has improved survival in cancer entities with actionable mutations but cannot capture oncogenic signaling that manifests at the protein level. Here, we report a prospective, real-world pan-cancer study profiling proteomes and phosphoproteomes of 1,998 tumor samples from adults and children with rare or advanced cancers enrolled in the German precision oncology programs DKFZ/NCT/DKTK MASTER, CATCH and INFORM and their molecular tumor boards (MTBs). We developed tumor proteome activity status (TOPAS) scores for 46 clinically relevant kinases, an immune activity score capturing antigen presentation and T-cell activation and identified therapeutically targetable cell-surface proteins for 94% of patients. These readouts enhance MTB recommendations by exposing actionable non-genomic kinase activity, refining interpretation of oncogenic genome alterations, and highlighting cell-surface treatment options. Three proof-of-concept analyses indicate clinical utility including kinase activity-stratified pazopanib response in sarcoma, immune activity score-tracked checkpoint-inhibitor outcomes pan-cancer, and a phosphoproteomic biomarker distinguishing EGFR-inhibitor response in chordoma.

cancer biology↗

bioRxiv2026

Alternative lengthening of telomeres stratifies complex karyotype sarcomas into distinct genomic and transcriptomic states

Complex karyotype sarcomas (CKS) are heterogeneous mesenchymal malignancies that typically lack recurrent actionable oncogenic drivers and remain therapeutically challenging. Loss of ATRX is a recurrent feature of CKS and defines a particularly high-risk subgroup. ATRX loss is also associated with activation of the alternative lengthening of telomeres (ALT) pathway, and ALT-positive sarcomas have been linked to poor clinical outcomes. However, the molecular underpinnings underlying ALT-status-dependent differences in CKS, as well as the therapeutic vulnerabilities associated with ALT, remain poorly defined. By integrating C-circle-based ALT detection across 776 sarcoma samples with multi-modal sequencing of five CKS subtypes, we find that ALT activity is associated with enriched hallmarks of genomic instability. ALT-positive transcriptomes are dominated by a coordinated DNA damage response and mitotic program, in contrast to oncogenic signaling pathways that drive TERT activation in ALT-negative tumors. Long-read sequencing reveals telomere repeat clusters and telomere-mediated healing at structural breakpoints in ALT-positive tumors. These events also occur on extrachromosomal DNA (ecDNA), linking ALT activity to ecDNA biology. Together, our findings position ALT status as an important stratifying feature of CKS and identify ALT-associated transcriptional programs as potential therapeutic targets.

cancer biology↗