# A Noninvasive Integrated Genomic Approach for Early Cancer Detection and Risk Stratification after Transplantation

> **NIH NIH R01** · STANFORD UNIVERSITY · 2020 · $606,977

## Abstract

PROJECT SUMMARY/ABSTRACT
Solid organ transplant recipients are an ideal population in which to study the link between oncogenic viral
infections and cancer due to the deep immunosuppression required to prevent allograft rejection, which
increases their risk of developing clinical complications such as infections and cancer. Our long-term goal is to
study the relations among immunosuppression, infections, and cancer using transplantation as a model system.
Our central hypothesis is that novel biomarkers of cancer risk such as detection of circulating tumor DNA,
sequencing of circulating cell-free DNA, and detailed immune profiling can be used for early cancer detection, to
identify changes in the virome that precede malignant transformation, and to quantify overall
immunosuppression. We will test our hypothesis via three specific aims: (1) To evaluate circulating tumor DNA
for early detection of post-transplant malignancies, focusing on post-transplant lymphoproliferative
disorders (PTLDs). We will evaluate the performance of CAPP-Seq, an ultra-sensitive assay for early cancer
detection, in existing cohorts of over 2000 heart and lung transplant recipients followed at Stanford University
and 6 collaborating sites. We will study patients with PTLDs to (a) determine the kinetics of emerging somatic
variants preceding tumor development, (b) define the window for accurate early prediction of cancer risk via
circulating tumor DNA, and (c) relate these findings to oncotropic viral expansion and immune system
suppression. Similar exploratory analyses will be performed in patients with post-transplant lung and colorectal
cancers. (2) To profile oncoviruses in cell-free DNA and evaluate integration sites as cancer risk
predictors. To distinguish features in the oncotropic virome preceding malignant transformation, we will enrich
oncoviral cell-free DNA to enable identification of human:virus gene fusion by deep sequencing, and will
determine whether read coverage is consistent with genome integration or with free DNA. We will then profile
DNA from primary tumors and cell-free DNA, and will compare integration site coverage in tumor subtypes. (3)
To quantify associations among immunosuppression, viral infection and cancer development. We will
perform novel immune profiling assays at defined time points following transplantation and will correlate results
with development of acute rejection, opportunistic infections, and cancer. Specifically, we will measure circulating
Anellovirus load, will infer immune cell subsets from RNA-seq, and will sequence the B-cell antibody heavy chain.
We will determine how these results relate to administered immunosuppression, and will build mathematical
models to predict risk of clinical complications. This contribution is significant because knowledge of the
molecular signatures associated with cancer risk and early detection may lead to novel ways to prevent, monitor,
and treat malignant disease. Our innovative approach, in...

## Key facts

- **NIH application ID:** 9882972
- **Project number:** 5R01CA229766-02
- **Recipient organization:** STANFORD UNIVERSITY
- **Principal Investigator:** Ash Arash Alizadeh
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $606,977
- **Award type:** 5
- **Project period:** 2019-03-01 → 2024-02-29

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9882972

## Citation

> US National Institutes of Health, RePORTER application 9882972, A Noninvasive Integrated Genomic Approach for Early Cancer Detection and Risk Stratification after Transplantation (5R01CA229766-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9882972. Licensed CC0.

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