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Detectable clonal mosaicism in blood as a biomarker of cancer risk in Fanconi anemia.
Reina-Castillón, Judith; Pujol, Roser; López-Sánchez, Marcos; Rodríguez-Santiago, Benjamín; Aza-Carmona, Miriam; González, Juan Ramón; Casado, José Antonio; Bueren, Juan Antonio; Sevilla, Julián; Badel, Isabel; Català, Albert; Beléndez, Cristina; Dasí, María Ángeles; Díaz de Heredia, Cristina; Soulier, Jean; Schindler, Detlev; Pérez-Jurado, Luis Alberto; Surrallés, Jordi.
Affiliation
  • Reina-Castillón J; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
  • Pujol R; Hospital del Mar Research Institute, Barcelona, Spain.
  • López-Sánchez M; Centro de Investigación Biomédica en Red de Enfermedades Raras, Barcelona, Spain.
  • Rodríguez-Santiago B; Centro de Investigación Biomédica en Red de Enfermedades Raras, Barcelona, Spain.
  • Aza-Carmona M; Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, Bellaterra, Spain.
  • González JR; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
  • Casado JA; Hospital del Mar Research Institute, Barcelona, Spain.
  • Bueren JA; Centre for Research in Environmental Epidemiology, ISGlobal, Barcelona, Spain.
  • Sevilla J; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
  • Badel I; Hospital del Mar Research Institute, Barcelona, Spain.
  • Català A; qGenomics Laboratory, Esplugues de Llobregat, Spain.
  • Beléndez C; Centro de Investigación Biomédica en Red de Enfermedades Raras, Barcelona, Spain.
  • Dasí MÁ; Department of Genetics and Microbiology, Universitat Autònoma de Barcelona, Bellaterra, Spain.
  • Díaz de Heredia C; Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona, Spain.
  • Soulier J; Centre for Research in Environmental Epidemiology, ISGlobal, Barcelona, Spain.
  • Schindler D; Centro de Investigación Biomédica en Red de Epidemiología y Salud Pública, Barcelona, Spain.
  • Pérez-Jurado LA; Centro de Investigación Biomédica en Red de Enfermedades Raras, Barcelona, Spain.
  • Surrallés J; Division of Hematopoietic Innovative Therapies, Centro de Investigaciones Energéticas, Medioambientales y Tecnológicas, Madrid, Spain.
Blood Adv ; 1(5): 319-329, 2017 Jan 24.
Article in En | MEDLINE | ID: mdl-29296947
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.

Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Etiology_studies / Risk_factors_studies Language: En Journal: Blood Adv Year: 2017 Document type: Article Affiliation country:

Full text: 1 Collection: 01-internacional Database: MEDLINE Type of study: Etiology_studies / Risk_factors_studies Language: En Journal: Blood Adv Year: 2017 Document type: Article Affiliation country: