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Peer-reviewedCC BYNature communications

Telomere length of both parents contributes to heritable POT1 cancer-predisposition syndrome.

  • Annika Martin1
  • Robert Lu1
  • Alise Blake2
  • Kim E Nichols2
  • Santiago E Sanchez3,4
  • Steven E Artandi4
  • Sharon A Savage5
  • Richa Sharma6
  • Dirk Hockemeyer7,8
8 affiliations
  1. 1Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA.
  2. 2Department of Oncology, St. Jude Children's Research Hospital, Memphis, TN, USA.
  3. 3Stanford Cancer Institute, Stanford University, Stanford, CA, USA.
  4. 4Medical Scientist Training Program, Stanford University, Stanford, CA, USA.
  5. 5Clinical Genetics Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, Bethesda, MD, USA.
  6. 6Department of Pediatric Hematology Oncology and Blood and Marrow Transplantation, Cleveland Clinic Children's, Cleveland, OH, USA.
  7. 7Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, CA, USA. [email protected].
  8. 8Innovative Genomics Institute, University of California, Berkeley, CA, USA. [email protected].
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Abstract

Germline and somatic mutations in POT1 promote oncogenesis by enabling aberrant telomere elongation. For inherited POT1 mutations, it remains unclear whether elongated telomeres are transmitted to the next generation and whether the inherited long telomeres elevate cancer risk. Using a nanopore sequencing approach that provides haplotype-specific telomere length resolution, we examined telomere inheritance in families carrying POT1 mutations. We found that offspring preferentially inherit their longest telomeres from the carrier parent, consistent with extensive germline telomere elongation, whereas comparatively short telomeres predominantly derive from the non-carrier parent. Analysis of carrier and non-carrier siblings demonstrated that telomeres from both parents are elongated in POT1 carriers, with preferential elongation of the shortest telomeres. These findings support a potential mechanism of genetic anticipation in which POT1 mutations progressively deplete short telomeres capable of enforcing telomere-based tumor suppression from the carrier germline. Therefore, telomeres inherited from both parents jointly shape telomere-based tumor suppressive barriers.

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Cite

BibTeXRIS
BibTeX
@article{martin2026telomere,
  title = {{Telomere length of both parents contributes to heritable POT1 cancer-predisposition syndrome.}},
  author = {Annika Martin and Robert Lu and Alise Blake and Kim E Nichols and Santiago E Sanchez and Steven E Artandi and Sharon A Savage and Richa Sharma and Dirk Hockemeyer},
  journal = {Nature communications},
  year = {2026},
  month = sep,
  doi = {10.1038/s41467-026-77414-2},
  url = {https://europepmc.org/article/MED/42875414},
  note = {CC BY},
}
RIS
TY  - JOUR
TI  - Telomere length of both parents contributes to heritable POT1 cancer-predisposition syndrome.
AU  - Annika Martin
AU  - Robert Lu
AU  - Alise Blake
AU  - Kim E Nichols
AU  - Santiago E Sanchez
AU  - Steven E Artandi
AU  - Sharon A Savage
AU  - Richa Sharma
AU  - Dirk Hockemeyer
PY  - 2026
DA  - 2026/09/14
JO  - Nature communications
DO  - 10.1038/s41467-026-77414-2
UR  - https://europepmc.org/article/MED/42875414
AB  - Germline and somatic mutations in POT1 promote oncogenesis by enabling aberrant telomere elongation. For inherited POT1 mutations, it remains unclear whether elongated telomeres are transmitted to the next generation and whether the inherited long telomeres elevate cancer risk. Using a nanopore sequencing approach that provides haplotype-specific telomere length resolution, we examined telomere inheritance in families carrying POT1 mutations. We found that offspring preferentially inherit their longest telomeres from the carrier parent, consistent with extensive germline telomere elongation, whereas comparatively short telomeres predominantly derive from the non-carrier parent. Analysis of carrier and non-carrier siblings demonstrated that telomeres from both parents are elongated in POT1 carriers, with preferential elongation of the shortest telomeres. These findings support a potential mechanism of genetic anticipation in which POT1 mutations progressively deplete short telomeres capable of enforcing telomere-based tumor suppression from the carrier germline. Therefore, telomeres inherited from both parents jointly shape telomere-based tumor suppressive barriers.
SN  - 2041-1723
ER  -