# Optimizing Ultrasensitive DNA methylation detection for lung cancer and other malignancies

> **NIH NIH U2C** · UNIVERSITY OF PITTSBURGH AT PITTSBURGH · 2022 · $658,591

## Abstract

This proposal for a Biomarker Characterization Center (BCC) for the Early Detection Research
Network (EDRN) seeks to improve the management of lung cancer through detection of cancer-
specific DNA methylation. This effort includes a Biomarker Development Laboratory (BDL) which
will optimize the methylation detection methods, implementation of these methods for clinical use
through a Biomarker Reference Laboratory (BRL) with a longstanding record of molecular testing
in a clinical setting, and an Administrative Core facilitating the interactions between the BDL and
BRL, and with other EDRN investigators and the NCI. Previous work by the applicants has
demonstrated the potential of DNA methylation detection for cancer diagnostics, and they have
developed extremely sensitive assays for the detection of hypermethylated DNA sequences and
optimized the isolation and processing of circulating cell-free DNA from tumors for these novel
assays. The approach has been used to detect circulating cancer-specific DNA methylation
changes for the early diagnosis of lung cancer in patients with screen-detected pulmonary
nodules. Although sensitivity and specificity of the assay are promising, additional improvements
in the performance are required for implementation of this approach in the setting of cancer
screening. In this BCC, detection of cancer-specific DNA methylation changes in the plasma will
be further improved, and new approaches developed and implemented to address the challenges
of ultrasensitive detection of DNA methylation in the blood. In addition, we will assess the potential
of these methods to detect other common and lethal malignancies. Our bioinformatic analysis of
DNA methylation from The Cancer Genome Atlas (TCGA) has identified novel highly frequent
cancer-specific methylation events common to all cancers, including lung cancer, that will be
developed into universal cancer detection assays. The use of TCGA data has also resulted in the
identification of other methylation alterations that allow determination of the origin (organ site) of
this cancer-specific signal. The combination of optimal sample processing, ultrasensitive
methylation detection, developed with universal cancer and histology specific loci detection, will
allow improved lung cancer early detection in the setting of CT screening and management of
detection of other cancer-specific DNA methylation from blood.

## Key facts

- **NIH application ID:** 10486258
- **Project number:** 1U2CCA271885-01
- **Recipient organization:** UNIVERSITY OF PITTSBURGH AT PITTSBURGH
- **Principal Investigator:** JAMES G. HERMAN
- **Activity code:** U2C (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $658,591
- **Award type:** 1
- **Project period:** 2022-09-16 → 2027-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10486258

## Citation

> US National Institutes of Health, RePORTER application 10486258, Optimizing Ultrasensitive DNA methylation detection for lung cancer and other malignancies (1U2CCA271885-01). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10486258. Licensed CC0.

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