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Updated: Dec 18, 2025

Rare Event Detection Using Error-corrected DNA and RNA Sequencing

Rare Event Detection Using Error-corrected DNA and RNA Sequencing

Published on: August 3, 2018

LC-FACSeq is a method for detecting rare clones in leukemia.

Eileen Y Hu^1,2, James S Blachly^1,3, Caner Saygin¹

¹Division of Hematology, Department of Internal Medicine and Comprehensive Cancer Center.

|June 20, 2020

Summary

A new method, limited-cell FACS sequencing (LC-FACSeq), allows sensitive detection and monitoring of rare cancer cells. This technique aids in understanding clonal evolution and therapy resistance in leukemias and other cancers.

Keywords:

Clonal selection Diagnostics Genetics Leukemias

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Comprehensive DNA Methylation Analysis Using a Methyl-CpG-binding Domain Capture-based Method in Chronic Lymphocytic Leukemia Patients

Comprehensive DNA Methylation Analysis Using a Methyl-CpG-binding Domain Capture-based Method in Chronic Lymphocytic Leukemia Patients

Published on: June 16, 2017

Area of Science:

Hematology
Oncology
Genomics

Background:

Monitoring rare cell populations is crucial for cancer management, particularly in cases of measurable residual disease (MRD).
Detecting genomic clonal resistance in MRD settings is challenging due to limited cancer cell numbers.
Current methods for analyzing rare cells in MRD are often resource-intensive and lack sensitivity.

Purpose of the Study:

To introduce limited-cell FACS sequencing (LC-FACSeq), a novel, highly sensitive method for rare cell analysis.
To demonstrate the utility of LC-FACSeq for characterizing clonal evolution and therapy resistance in leukemias.
To establish LC-FACSeq as a generalizable technique for monitoring blood and marrow infiltrating cancers.

Main Methods:

Development of limited-cell FACS sequencing (LC-FACSeq) for rare cell characterization.
Application of LC-FACSeq for broad multigene panel analysis.
Utilizing LC-FACSeq to monitor sequential mutations in chronic lymphocytic leukemia patients undergoing ibrutinib treatment.

Main Results:

LC-FACSeq provides a reproducible and highly sensitive method for characterizing clonal evolution in rare cells.
The technique successfully identified genomic resistance mechanisms in leukemia.
LC-FACSeq enabled monitoring of acquired mutations and clonal evolution during long-term ibrutinib therapy in chronic lymphocytic leukemia.

Conclusions:

LC-FACSeq is a powerful tool for detecting, characterizing, and monitoring rare cell populations in various cancers.
This method enhances the understanding of disease mechanisms and informs clinical decision-making in MRD.
LC-FACSeq offers a generalizable approach for monitoring therapeutic resistance and clonal dynamics in hematologic malignancies and other infiltrating cancers.