# DICER-Dx: The First Liquid Biopsy for Early Detection and Monitoring of DICER1 Syndrome Pediatric Cancers

> **NIH NIH R44** · RESOURCEPATH, LLC · 2020 · $747,004

## Abstract

PROJECT SUMMARY/ABSTRACT
 Pleuropulmonary blastoma (PPB) is the most common lung cancer of childhood, and the most common
manifestation of DICER1 syndrome; a genetic predisposition to early-onset embryonal tumors of multiple organ
sites. The syndrome is defined by germline mutations in the DICER1 gene (OMIM #606241). In addition to
PPB, the spectrum of syndromic neoplasias includes ovarian Sertoli-Leydig cell tumor, cystic nephroma and
renal sarcoma or Wilms tumor, embryonal rhabdomyosarcoma, nodular hyperplasia and carcinoma of the
thyroid gland, nasal chondromesenchymal hamartoma, pituitary blastoma and pineoblastoma. PPB diagnosed
in its earliest, cystic stage, called Type I, is treated by surgical resection with or without adjuvant
chemotherapy. There is no reliable way to distinguish patients who will recur without adjuvant therapy from
those who would not. More advanced PPB (Type II or Type III) is treated by surgery plus a standard multidrug
chemotherapy regime. Tumor resistance to standard chemotherapy indicates more intense treatments, but
currently, response to therapy can be assessed only by imaging studies, which have limited sensitivity. Lack of
an effective test for residual disease or therapy resistance is a major barrier to improving the survivals of
children with PPB and results in unnecessary treatment-related morbidities.
 Genetic pathogenesis in DICER1 syndrome is unique and offers a solution to the detection problems that
hinder clinical management. From tumor sequencing studies, we know that virtually all DICER1 syndrome
cancers carry a second, somatically acquired DICER1 mutation. These are invariably missense mutations,
restricted to just five codons of the gene; the DICER1 hotspot mutations. The hotspot mutations are promising
as potential biomarkers because they are so unambiguously associated with DICER1 syndrome cancers.
 ResourcePath, LLC is developing DICER-Dx, the first biomarker assay for DICER1 syndrome cancers.
DICER-Dx is a panel of droplet digital PCR (ddPCR) assays for ultra-sensitive detection of DICER1 hotspot
mutations in circulating tumor DNA (ctDNA). It has the potential to transform standards of care for children with
DICER1 syndrome cancers by: 1) Clarifying the differential diagnosis of Type I PPB vs. benign lung cysts; 2)
Guiding treatment decisions for children with PPB or other DICER1 syndrome tumors, e.g., by detecting occult
residual disease after surgical removal of Type I PPB; 3) Monitoring tumor response to standard chemotherapy
for Type II/III PPB so that timely changes in treatment can be made if needed, and; 4) Enabling early detection
of any disease recurrence after treatment is completed. DICER1-Dx testing for ctDNA will become an essential
component of treatment and biology studies conducted by the International PPB Registry. DICER-Dx assays
will also become an indispensable tool to assess the efficacy of new therapeutics for DICER1 syndrome
cancers in preclinical research and clinical tr...

## Key facts

- **NIH application ID:** 9968173
- **Project number:** 5R44CA228850-03
- **Recipient organization:** RESOURCEPATH, LLC
- **Principal Investigator:** Dana Ashley Hill
- **Activity code:** R44 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $747,004
- **Award type:** 5
- **Project period:** 2018-05-07 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9968173

## Citation

> US National Institutes of Health, RePORTER application 9968173, DICER-Dx: The First Liquid Biopsy for Early Detection and Monitoring of DICER1 Syndrome Pediatric Cancers (5R44CA228850-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9968173. Licensed CC0.

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