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Updated: Sep 11, 2025

Characterizing Mutational Load and Clonal Composition of Human Blood
Published on: July 11, 2019
Uniquely high spontaneous mutational load in blood cells of XP-C patients
Gordon Fan-Huang1, Elizabeth L Schmidt2,3, Moonsook Lee1
1Department of Genetics, Albert Einstein College of Medicine, Bronx NY 10461, USA.
Abstract:
We discovered a uniquely high spontaneous somatic mutational load in peripheral blood mononuclear cells (PBMCs) of Xeroderma Pigmentosum group C (XP-C) patients, characterized by elevated single nucleotide variants associated with mutation signatures SBS8 and SBS32, as well as an enrichment of single-nucleotide cytosine deletions. This hypermutability was markedly lower in fibroblasts, suggesting a replication-dependent mechanism of mutagenesis due to deficient global genome nucleotide excision repair (GG-NER). Our findings reveal distinct molecular subtypes within XP defined by spontaneous mutational load in normal blood cells and demonstrate that the exceptionally high mutation burden in XP-C leukemia originates from mutations already present prior to malignant transformation.
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