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Detectable clonal mosaicism in blood as biomarker of cancer risk in Fanconi anemia

ABSTRACT: Detectable clonal mosaicism for large chromosomal events has been associated with aging and increased risk of hematological and some solid cancers. We hypothesized that genetic cancer predisposition disorders such as Fanconi anemia (FA) could manifest a high rate of chromosomal mosaic events (CMEs) in peripheral blood, which could be used as early biomarkers of cancer risk. We studied the prevalence of CMEs by Single-Nucleotide Polymorphism (SNP) array in 130 FA patients’ blood DNA and their impact on cancer risk. We detected 51 CMEs (4.4-159Mb in size) in 16/130 patients (12.3%), 9 of them with multiple CMEs. Most frequent events were gains at 3q (n=6) and 1q (n=5), both previously associated with leukemia, as well as rearrangements with breakpoint clustering within the Major Histocompatibility Complex (MHC) locus (p=7.3x10-9). Compared to 15743 age-matched population controls, FA patients had 126-140 higher risk of detectable CMEs in blood (p<2.2x10-16). Prevalent and incident hematologic and solid cancers were more common in CME carriers (OR=11.6, CI95%=3.4-39.3, p=2.8x10-5), leading to poorer prognosis. The age-adjusted hazard risk (HR) of having cancer was almost 5 times higher in FA individuals with CMEs than in those without CMEs. Regarding survival, the HR of dying was 4 times higher in FA individuals having CMEs (HR=4.0, CI95%=2.0-7.9, p=5.7x10-5). Therefore, our data suggests that molecular karyotyping with SNP arrays in easy-to-obtain blood samples could be used for better monitoring of bone marrow clonal events, cancer risk and overall survival of FA patients.

ORGANISM(S): Homo sapiens

PROVIDER: GSE93692 | GEO | 2017/02/24

SECONDARY ACCESSION(S): PRJNA362266

REPOSITORIES: GEO

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Detectable clonal mosaicism in blood as biomarker of cancer risk in Fanconi anemia

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