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. 2023 Feb;200(4):489-493.
doi: 10.1111/bjh.18543. Epub 2022 Nov 9.

Inherited cancer predisposing mutations in patients with therapy-related myeloid neoplasms

Andrew J Shih  1 , Tomi Jun  2 , Andrew D Skol  3 , Riyue Bao  4   5 , Lei Huang  6 , Sapana Vora  3 , Megan E McNerney  3   7 , Eric A Hungate  3 , Michelle M Le Beau  8 , Richard A Larson  8 , Aaron Elliott  9 , Hsiao-Mei Lu  9 , Robert Huether  9 , Felicia Hernandez  9 , Friedrich Stölzel  10 , James M Allan  11 , Kenan Onel  2   12
Affiliations

Inherited cancer predisposing mutations in patients with therapy-related myeloid neoplasms

Andrew J Shih et al. Br J Haematol. 2023 Feb.

Abstract

Some patients with therapy-related myeloid neoplasms (t-MN) may have unsuspected inherited cancer predisposition syndrome (CPS). We propose a set of clinical criteria to identify t-MN patients with high risk of CPS (HR-CPS). Among 225 t-MN patients with an antecedent non-myeloid malignancy, our clinical criteria identified 52 (23%) HR-CPS patients. Germline whole-exome sequencing identified pathogenic or likely pathogenic variants in 10 of 27 HR-CPS patients compared to 0 of 9 low-risk CPS patients (37% vs. 0%, p = 0.04). These simple clinical criteria identify t-MN patients most likely to benefit from genetic testing for inherited CPS.

Keywords: cancer predisposition; germline; leukaemia; therapy-related myeloid neoplasm; whole-exome sequencing.

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Conflict of interest statement

Competing Interests

All authors declare no conflicts of interest or competing financial interests.

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