CHIP Mutations in Hematology: The Silent Forecasters of Risk

In the world of hematology, not all mutations signal malignancy. Some are whispers—subclinical, silent, yet powerfully predictive. These are CHIP mutations, and they are changing the way we understand aging, cancer risk, and therapy-related complications.
At the Fortis Institute of Genomic Medicine, we don’t just listen to these whispers—we decode them.

What is CHIP—and Why Should We Care?

Clonal Hematopoiesis of Indeterminate Potential (CHIP) refers to the presence of somatic mutations in blood-forming cells in individuals without overt hematologic malignancy. These mutations—often in genes like DNMT3A, TET2, ASXL1, TP53, PPM1D, SRSF2, among others—reflect the expansion of mutated clones in the bone marrow.

Initially considered benign, CHIP is now recognized as a premalignant state with broad implications across oncology, cardiology, and transplant medicine.

Why CHIP Testing Matters in Clinical Practice

1. Early Detection of Myeloid Neoplasms

   CHIP mutations can precede acute myeloid leukemia (AML), MDS, or MPN by years. In fact, studies show that 10–20% of AML cases arise from pre-existing CHIP clones.

2. Risk Stratification in Solid Tumor Survivors

   Patients treated with alkylating agents, PARP inhibitors, or radiotherapy—especially for breast, ovarian, or prostate cancers—may harbor therapy-related CHIP. These individuals are at higher risk of developing secondary hematologic malignancies.

3. Cardiovascular Implications

   Mutations in TET2 and DNMT3A are linked to increased risk of atherosclerosis, heart failure, and stroke, due to enhanced inflammatory signaling in vascular endothelium.

4. Transplant Considerations

   CHIP mutations in stem cell donors are associated with poor engraftment, donor-derived leukemia, and altered immune reconstitution. Our team routinely screens for CHIP in both autologous and allogeneic transplant settings.

5. CHIP in ctDNA: A Diagnostic Pitfall

   In patients undergoing liquid biopsy, CHIP-derived mutations can be mistaken for tumor mutations, especially in TP53 or JAK2. Fortis employs dual-layered genomic filtering to accurately distinguish tumor-derived vs hematopoietic-derived variants.

CHIP in India: A Rising Concern

In our large-scale AML NGS study, we observed a higher prevalence of CHIP-associated mutations in Indian patients, including young adults. This raises important questions about environmental exposures, delayed diagnoses, and age-related clonal expansion unique to our population.

We’ve also implemented longitudinal CHIP monitoring in cancer survivors—an initiative currently unique to Fortis and aligned with the 2025 NCCN recommendations.

Fortis Genomics Advantage: Turning Risk Into Resilience

• Oncomine Myeloid GX v2 CHIP-focused screening with ultrafast TAT
• Integrated reporting with AI-assisted CHIP categorization
• CHIP stratification reports for oncologists, cardiologists, and BMT physicians
• ctDNA vs CHIP disambiguation using paired tissue and blood sequencing
• Prospective CHIP surveillance in high-risk cohorts (e.g., post-PARPi, post-chemotherapy)

From Hidden Mutation to Clinical Mission

CHIP may not always lead to cancer—but ignoring it is no longer an option. As precision medicine evolves, CHIP testing is now as essential as any tumor marker.

At the Fortis Institute of Genomic Medicine, we’re proud to be among the first in India to integrate CHIP testing into real-world workflows. Because in modern hematology, prevention isn’t just better than cure—it’s powered by genomics.