Web of Science: 5 citations, Google Scholar: citations,
Detectable clonal mosaicism in blood as biomarker of cancer risk in Fanconi anemia
Reina-Castillón, Judith (Universitat Pompeu Fabra. Departament de Ciències Experimentals i de la Salut)
Pujol i Calvet, M. Roser (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)
López-Sánchez, Marcos (Hospital del Mar (Barcelona, Catalunya))
Surrallés i Calonge, Jordi (Universitat Autònoma de Barcelona. Departament de Genètica i de Microbiologia)

Date: 2016
Abstract: 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 × 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 × 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 × 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 × 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.
Note: Altres ajuts: Juan de la Cierva postdoctoral fellowship (JCI-2011-10660); Marató de TV3 (project 464/C/2012)
Note: Número d'acord de subvenció EC/H2020/703521
Note: Número d'acord de subvenció MICINN/FPU13/00782
Note: Número d'acord de subvenció MICINN/CB06/07/0023
Note: Número d'acord de subvenció MINECO/SAF2012-31881
Note: Número d'acord de subvenció MINECO/SAF2015-64152-R
Note: Número d'acord de subvenció MINECO/MDM-2014-0370
Note: Número d'acord de subvenció AGAUR/2009/SGR-489
Note: Número d'acord de subvenció AGAUR/2014/SGR-317
Note: Número d'acord de subvenció AGAUR/2014/SRG-1468
Rights: Tots els drets reservats.
Language: Anglès.
Document: article ; recerca ; publishedVersion
Subject: Fanconi anemia patients ; Bone marrow clonal abnormalities ; Cancer risk ; Molecular karyotyping ; Cytogenetic clonal mosaicism
Published in: Blood, Advances, Vol. 1 (2017) , p. 319-329

DOI: 10.1182/bloodadvances.2016000943
PMID: 29296947


11 p, 1.8 MB

The record appears in these collections:
Articles > Research articles
Articles > Published articles

 Record created 2017-04-10, last modified 2019-02-02



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