# Predoctoral to Postdoctoral Research Training in ctDNA Biology for Liquid Biopsy of Cancer

> **NIH NIH F99** · UNIVERSITY OF CALIFORNIA LOS ANGELES · 2022 · $41,244

## Abstract

PROJECT SUMMARY/ABSTRACT
Circulating tumor DNA (ctDNA) which mirrors the parental tumor, is present in the plasma of non-small cell lung
carcinoma (NSCLC) patients. Liquid biopsy analysis of ctDNA allows early detection and genetic monitoring.
However, current PCR-based liquid biopsy methods often have difficulty detecting ctDNA due to low copies in
circulation. In contrast, the electric field-induced release and measurement liquid biopsy (eLB) platform, detects
mutant EGFR (L858R, exon19del, T790M) ctDNA with a >90% tissue-genotype concordance in <50ul of
unprocessed plasma of NSCLC patients. Preliminary data demonstrate that the ctDNA detected by eLB may be
ultrashort single-stranded ctDNA (usssctDNA) which contrasts the typically described 160-basepair
internucleosomal double-stranded ctDNA. This new subpopulation is undetectable through PCR-based liquid
biopsy methods due to size-selection bias. The goal of the F99 Phase is to use usssctDNA-seq, a novel NGS
pipeline, to explore if NSCLC plasma contains high quantities of ctDNA that are ultrashort and single-stranded.
This pipeline consists of a usssctDNA-specific extraction, library preparation, deep sequencing, and bioinformatic
analysis. To verify, 80 late-stage NSCLC EGFR-mutated plasma samples will undergo usssctDNA-seq. The
discovery of usssctDNA will open up a wealth of previously unnoticed information leading to improved treatment
and survival of NSCLC patients. Afterward, during the K00 Phase, the trainee hopes to explore the biological
origins of biofluid ctDNA and the incorporation of usssctDNA into modern multi-analyte approaches for pan-
cancer detection. This will involve training in new skills such as organoid modeling, methylation and leukocyte
sequencing, and bioinformatic machine learning at a world-leading cancer-oriented institute. Ultimately, the goal
of this proposed F99/K00 project will to prepare the trainee for a career in cancer research with an expertise in
liquid biopsy and cell-free DNA biology.

## Key facts

- **NIH application ID:** 10470351
- **Project number:** 5F99CA264398-02
- **Recipient organization:** UNIVERSITY OF CALIFORNIA LOS ANGELES
- **Principal Investigator:** Jordan C Cheng
- **Activity code:** F99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $41,244
- **Award type:** 5
- **Project period:** 2021-09-01 → 2023-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10470351

## Citation

> US National Institutes of Health, RePORTER application 10470351, Predoctoral to Postdoctoral Research Training in ctDNA Biology for Liquid Biopsy of Cancer (5F99CA264398-02). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10470351. Licensed CC0.

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