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Evolutionary Relationships through Genome Comparisons

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Genome comparison is one of the excellent ways to interpret the evolutionary relationships between organisms. The basic principle of genome comparison is that if two species share a common feature, it is likely encoded by the DNA sequence conserved between both species. The advent of genome sequencing technologies in the late 20th century enabled scientists to understand the concept of conservation of domains between species and helped them to deduce evolutionary relationships across diverse...

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Live Imaging Followed by Single Cell Tracking to Monitor Cell Biology and the Lineage Progression of Multiple Neural Populations

Live Imaging Followed by Single Cell Tracking to Monitor Cell Biology and the Lineage Progression of Multiple Neural Populations

Published on: December 16, 2017

Integration of multiple lineage measurements from the same cell reconstructs parallel tumor evolution.

Lennart Kester¹, Buys de Barbanson^1,2, Anna Lyubimova¹

¹Oncode Institute, Hubrecht Institute-KNAW (Royal Netherlands Academy of Arts and Sciences), 3584 CT Utrecht, the Netherlands.

|February 13, 2023

Summary

This study used colon cancer organoids and single-cell sequencing to track tumor evolution over six months. Researchers identified recurrent chromosome 4 and 18 loss, a key finding for understanding colorectal cancer progression.

Keywords:

clonal evolution single-cell whole-genome sequencing tumor heterogeneity

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Comparative Lesions Analysis Through a Targeted Sequencing Approach

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Published on: November 5, 2019

Area of Science:

Cancer Biology
Genomics
Evolutionary Biology

Background:

Intra-tumor heterogeneity (ITH) and tumor evolution are critical challenges in cancer research.
Organoid models offer a promising platform for studying these complex processes.
Single-cell sequencing technologies enable high-resolution analysis of cellular diversity within tumors.

Purpose of the Study:

To reconstruct colon cancer evolution at high resolution using organoid models.
To identify the order and recurrence of genomic aberrations during tumor development.
To investigate the clinical relevance of observed genomic events in colorectal cancer.

Main Methods:

Evolved a colon cancer organoid model for 100 generations (6 months).
Integrated single-cell whole-genome sequencing (WGS) and viral lineage tracing.
Analyzed 1,641 single cells across 12 time points for clone size, SNVs, CNVs, and viral barcodes.

Main Results:

Constructed high-resolution clonal evolution trees.
Characterized the sequential order of chromosomal aberrations.
Observed recurrent loss of chromosome 4 after chromosome 18 loss in four distinct tumor clones.
Validated SNV and CNV findings against a colorectal cancer patient cohort, noting 29.6% co-occurrence of chromosome 4 and 18 loss.

Conclusions:

Organoid evolution models with integrated single-cell sequencing provide a powerful approach to study tumor evolution.
Identified a potentially clinically relevant recurrent genomic aberration (chr18 loss followed by chr4 loss) in colorectal cancer.
This methodology can identify significant genomic events driving tumor development and heterogeneity.