# Genomics Core

> **NIH NIH P01** · SLOAN-KETTERING INST CAN RESEARCH · 2022 · $514,327

## Abstract

ABSTRACT
The objectives of the Genomics Core are 1) to perform prospective and retrospective molecular analysis of
prostate tumors, cell-free DNA (cfDNA) and germline DNA to facilitate the aims of the P01 and 2) to facilitate
sharing of genomic data and linked clinical annotation among the P01 investigators and with the broader
scientific community. To achieve these objectives, the Genomics Core includes personnel trained in cancer
genetics, surgical pathology, biostatistics, bioinformatics, and genomic data sharing. The Genomics Core has
three aims. First, to aid in the identification of germline mutations associated with increased heritable risk or
poor long-term clinical outcomes, the Genomics Core will conduct targeted sequencing of 250 DNA damage
repair (DDR) pathway genes or WES of prostate cancer tumors and matched germline DNA (Project 1) from
men with prostate cancer for whom we have long-term clinical outcomes data. To further facilitate the
identification of novel germline mutations that associate with increased heritable risk or poor clinical outcomes,
all sequencing data generated as part of this P01 will be integrated in real-time with published datasets and
unpublished genomic data from ongoing profiling initiatives at Memorial Sloan Kettering Cancer Center (MSK-
IMPACT) and Dana-Farber Cancer Institute (DFCI-Profile). Second, the core will explore mechanisms of
treatment resistance by analyzing tumors and cfDNA collected before and after PARP inhibitor treatment from
patients enrolled on the MetaCURE clinical trial platform (Project 2). This latter aim required the Genomics
Core to develop a cfDNA assay (MSK-ACCESS) that could be used to monitor patients for minimal residual
disease and could also identify mutations that mediate response and resistance to PARP inhibition. Third, the
core will facilitate data sharing both within the P01 and with the broader research community, including the
NCI. All three research projects are highly integrated with and rely extensively on the Genomics Core to
achieve their proposed aims. More specifically, the core will assist Project 1 by sequencing (targeted and
whole exome) germline and, in some cases, matched tumor DNA from several large cohorts of annotated
patient samples to identify alterations in DDR pathway genes. The core will also provide real-time access to
the germline data generated by MSK-IMPACT and DFCI-Profile. The core will assist Project 2 by screening
patients for DDR aberrations and with the analysis of tumor samples and cfDNA collected before and after
PARP inhibitor treatment to monitor treatment response and to explore mechanisms of drug resistance. The
core will work with Project 3 to perform molecular analyses of cells engineered to harbor deleterious BRCA2
or ATM alleles or in which ATM or CDH1 have been deleted. Finally, the Genomics Core will help all three
projects make predictions about the pathogenicity of individual mutations to facilitate data interpretation, stud...

## Key facts

- **NIH application ID:** 10495181
- **Project number:** 5P01CA228696-03
- **Recipient organization:** SLOAN-KETTERING INST CAN RESEARCH
- **Principal Investigator:** David B. Solit
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $514,327
- **Award type:** 5
- **Project period:** 2019-09-01 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10495181

## Citation

> US National Institutes of Health, RePORTER application 10495181, Genomics Core (5P01CA228696-03). Retrieved via AI Analytics 2026-05-22 from https://api.ai-analytics.org/grant/nih/10495181. Licensed CC0.

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