Association of high-dose radioactive iodine therapy with PPM1D-mutated clonal hematopoiesis in older individuals

Jaeryuk Kim^{1

2

3

4}, Sungwoo Bae⁵, Jaeyong Choi^{1

2

3

6}, Sun-Wha Im⁶, Bukyoung Cha^{1

3}, Gyeongseo Jung⁷, Sun Wook Cho⁷, Eul-Ju Seo⁴, Young Ah Lee^{1

8}, Jin Chul Paeng⁹, Young Joo Park^{1

7

10}, Jong-Il Kim^{1

2

3

11}

Affiliations

¹ Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Korea.
² Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.
³ Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Korea.
⁴ Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
⁵ Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Korea.
⁶ Department of Biochemistry and Molecular Biology, Kangwon National University School of Medicine, Gangwon, Korea.
⁷ Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
⁸ Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Korea.
⁹ Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Korea.
¹⁰ Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea.
¹¹ Cancer Research Institute, Seoul National University, Seoul, Korea.

PMID: 40569832
DOI: 10.1002/1878-0261.70078

Association of high-dose radioactive iodine therapy with PPM1D-mutated clonal hematopoiesis in older individuals

Jaeryuk Kim et al. Mol Oncol. 2025.

. 2025 Jun 26.

doi: 10.1002/1878-0261.70078. Online ahead of print.

Authors

Affiliations

¹ Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Korea.
² Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.
³ Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Korea.
⁴ Department of Laboratory Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea.
⁵ Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul, Korea.
⁶ Department of Biochemistry and Molecular Biology, Kangwon National University School of Medicine, Gangwon, Korea.
⁷ Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Korea.
⁸ Department of Pediatrics, Seoul National University Children's Hospital, Seoul National University College of Medicine, Seoul, Korea.
⁹ Department of Nuclear Medicine, Seoul National University Hospital, Seoul, Korea.
¹⁰ Department of Molecular Medicine and Biopharmaceutical Sciences, Graduate School of Convergence Science and Technology, Seoul National University, Seoul, Korea.
¹¹ Cancer Research Institute, Seoul National University, Seoul, Korea.

PMID: 40569832
DOI: 10.1002/1878-0261.70078

Abstract

While radioactive iodine therapy (RAIT) has been an effective treatment for thyroid cancer, its link to clonal hematopoiesis (CH) has been yet underexplored. In this study, error-corrected sequencing (median depth: 1926×) of 93 CH-related genes was performed from the blood samples of 358 thyroid cancer patients, including 110 controls (no RAIT) and 248 RAIT recipients. RAIT recipients were stratified into low- and high-dose groups using a 7.4 GBq cutoff. Multivariable logistic regression revealed that the high-dose group had a higher CH prevalence with variant allele frequency (VAF) higher than 2% compared to controls, especially in patients aged ≥50 (OR = 2.44, CI = 1.04-6.00, P = 0.04). Thirteen genes had mutations with VAF >2%, with DNMT3A, TET2, and PPM1D being the most common. Notably, only the PPM1D mutations were significantly linked to RAIT, occurring more frequently in the high-dose group (13%) compared to the low-dose group (5%) or controls (2%) at a VAF cutoff of 0.5%. In silico analyses indicated that truncating PPM1D mutations confer a selective advantage under high-dose RAIT and with older age. Although the prognostic implications of PPM1D-mutated CH remain to be further elucidated, these findings offer valuable insights for optimizing RAIT dosing in thyroid cancer patients.

Keywords: PPM1D mutations; error‐corrected next‐generation sequencing; radioactive iodine therapy; therapy‐related clonal hematopoiesis; thyroid cancer.

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References

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Association of high-dose radioactive iodine therapy with PPM1D-mutated clonal hematopoiesis in older individuals

Affiliations

Association of high-dose radioactive iodine therapy with PPM1D-mutated clonal hematopoiesis in older individuals

Authors

Affiliations

Abstract

References

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