ABOUT THE EVENT
Date: Tuesday, October 13, 2026 8am PDT
Event Location: Virtual
Chromosomal instability drives cancer progression. Structural instability, marked by translocations and deletions, has been studied for decades. Numerical instability, the gain or loss of whole chromosomes, has received far less attention despite its frequency in myeloid malignancies such as acute myeloid leukemia (AML), a blood cancer marked by rapid, uncontrolled growth of immature myeloid cells.
In this live webinar, Dr. Asif Javed will present new work on whole-chromosome gains, or trisomies, in AML. Bulk DNA sequencing across three patient cohorts identified regulatory gene mutations, including ASXL1, SRSF2, STAG2, and EZH2, enriched in trisomy-positive patients. Single-cell DNA sequencing on Mission Bio’s Tapestri platform, using a custom targeted panel, then resolved mutations and chromosome copy number within the same cells. This reconstructed clonal phylogenies and pinpointed when each mutation arose relative to the chromosome gain.
Combined with a CRISPR screen and evolutionary modeling, the results support a cumulative model in which regulatory gene disruption progressively destabilizes chromosome segregation until a chromosome is gained. Layering single-cell data onto bulk sequencing and functional screens provides a more complete view of how numerical instability may emerge and evolve while resolving the order of mutations and chromosome gains at single-cell resolution.
Together, this approach can help reveal how genomic instability develops within individual cells and provide new insight into the mechanisms underlying disease progression.
Key learnings
- Bulk sequencing across three independent cohorts of myeloid malignancies (1,650 cytogenetically normal and 229 trisomy patients) identified regulatory gene mutations associated with whole-chromosome gains, with ASXL1, SRSF2, STAG2, and EZH2 remaining significant after multiple-testing correction.
- Single-cell DNA sequencing on Mission Bio’s Tapestri platform profiled 51,092 cells across 16 AML patients to reconstruct clonal phylogenies, showing regulatory gene mutations typically arise before the chromosome gain.
- In 71% of trisomy-positive cases, more than one regulatory mutation occurred before or within the same clonal branch as the chromosome gain supporting a cumulative mechanism rather than a single driver mutation.
- CRISPR screen data and evolutionary simulation modeling support a model in which progressive disruption of transcription and chromatin regulation destabilizes chromosome segregation over time.
