# Cancer Genetics of Short Telomere Syndromes

> **NIH NIH R01** · JOHNS HOPKINS UNIVERSITY · 2022 · $446,652

## Abstract

Project Summary
This application focuses on defining the genetic basis of cancer prone syndromes caused by abnormally short
telomere length. Mutations in telomerase enzyme components are their best known cause, but in nearly half of
autosomal dominant families, the mutant gene is not known. We have previously shown that these disorders
are the most common premature aging syndromes with a majority of individuals manifesting symptoms in mid
to late adulthood. Myelodysplastic syndrome and acute myeloid leukemia are the most common STS cancers;
they have a 2000-fold increased incidence in patients with short telomere syndromes and comprise at least
half of the cancers diagnosed in this population. Mutations in the telomerase genes are also the most
prevalent cause of familial myelodysplastic syndrome and acute myeloid leukemia. Recognizing patients with
telomere-mediated cancers is critical for clinical management since they are highly prone to toxicities from
conventional therapies. They also often rely on stem cell transplantation from related donors as a therapy,
making it essential to identify the genetic etiology in order to avoid donor-derived complications. This proposal
builds on a long-standing program at Johns Hopkins that is focused on defining the genetic basis of short
telomere syndromes and implementing that knowledge into clinical paradigms that advance patient care. It
includes one of the largest and best characterized populations of short telomere syndrome patients in the
world. Our goal is to identify new Mendelian cancer predisposing genes through family-based studies and to
understand the role of these genes in telomere length maintenance. Our findings have direct relevance for
understanding the genetic basis of cancer, advancing precision medicine paradigms for myelodysplastic
syndrome and acute myeloid leukemia patients, while deepening the fundamental understanding of telomerase
biology and telomere maintenance mechanisms.

## Key facts

- **NIH application ID:** 10434717
- **Project number:** 5R01CA225027-05
- **Recipient organization:** JOHNS HOPKINS UNIVERSITY
- **Principal Investigator:** Mary Y Armanios
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $446,652
- **Award type:** 5
- **Project period:** 2018-07-03 → 2024-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10434717

## Citation

> US National Institutes of Health, RePORTER application 10434717, Cancer Genetics of Short Telomere Syndromes (5R01CA225027-05). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10434717. Licensed CC0.

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