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

# metadata.dc.description.abstract[].value
Detectable clonal mosaicism for large chromosomal events has
                been associated with aging and an 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
                (4.4-159 Mb in size) in 16 out of 130 patients (12.3%), of which
                9 had multiple CMEs. The 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 locus (P = 7.3 x
                10(-9)). Compared with 15 743 age-matched population controls,
                FA patients had a 126 to 140 times higher risk of detectable
                CMEs in blood (P < 2.2 x 10(-16)). Prevalent and incident
                hematologic and solid cancers were more common in CME carriers
                (odds ratio [OR] = 11.6, 95% confidence interval [CI] =
                3.4-39.3, P = 2.8 x 10(-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, 95% CI = 2.0-7.9, P = 5.7
                x 10(-5)). Therefore, our data suggest 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.

# metadata.dc.relation.isformatof[].value
Reproducció del document publicat a:
                http://dx.doi.org/10.1182/bloodadvances.2016000943

# metadata.dc.rights[].value
(c)  American Society of Hematology, 2017

# metadata.dc.source[].value
Articles publicats en revistes (ISGlobal)

# metadata.dc.title[].value
Detectable clonal mosaicism in blood as a biomarker of cancer
                risk in Fanconi anemia