Chromosome fragility in patients with Fanconi anaemia: diagnostic implications and clinical impact

Castellà, María; Pujol, Roser; Callén, Elsa; Ramı́rez, Marı́a José; Casado, José Antonio; Talavera, María; Ferró, Teresa; Muñoz, Arturo; Sevilla, Julián; Madero, Luís; Cela, Elena; Beléndez, Cristina; Heredia, Cristina Díaz de; Olivé, T; Toledo, José Sánchez de; Badell, Isabel; Estella, Jesús; Dasí, Ángeles; Rodríguez-Villa, Antonia; Gómez, Pedro; Tapia, Maria C.; Molinés, Antonio; Figuera, Á; Bueren, Juan A.; Surrallés, Jordi

doi:10.1136/jmg.2010.084210

Cited by 52 publications

(86 citation statements)

References 36 publications

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“…Reasons for this nonworsening are not clear. Somatic mosaicism in hematopoietic cells could be an explanation [15][16][17][18][19]. In our cohort phenotypic and/or genetic reversion was shown in 6 of the 11 patients who improved hematologically.…”

Section: Discussionmentioning

confidence: 84%

Somatic, hematologic phenotype, long‐term outcome, and effect of hematopoietic stem cell transplantation. An analysis of 97 Fanconi anemia patients from the Italian national database on behalf of the Marrow Failure Study Group of the AIEOP (Italian Association of Pediatric Hematology–Oncology)

et al. 2016

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We analyzed 97 Fanconi anemia patients from a clinic/biological database for genotype, somatic, and hematologic phenotype, adverse hematological events, solid tumors, and treatment. Seventy‐two patients belonged to complementation group A. Eighty percent of patients presented with mild/moderate somatic phenotype and most with cytopenia. No correlation was seen between somatic/hematologic phenotype and number of missense mutations of FANCA alleles. Over follow‐up, 33% of patients improved or maintained mild/moderate cytopenia or normal blood count, whereas remaining worsened cytopenia. Eleven patients developed a hematological adverse event (MDS, AML, pathological cytogenetics) and three developed solid tumors. 10 years cumulative risk of death of the whole cohort was 25.6% with median follow‐up 5.8 years. In patients eligible to hematopoietic stem cell transplantation because of moderate cytopenia, mortality was significantly higher in subjects transplanted from matched unrelated donor over nontransplanted subjects, whereas there was no significant difference between matched sibling donor transplants and nontransplanted patients. In patients eligible to transplant because of severe cytopenia and clonal disease, mortality risk was not significantly different in transplanted from matched unrelated versus matched sibling donor versus nontransplanted subjects. The decision to transplant should rely on various elements including, type of donor, HLA matching, patient comorbidities, impairment, and clonal evolution of hematopoiesis. Am. J. Hematol. 91:666–671, 2016. © 2016 Wiley Periodicals, Inc.

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Section: Discussionmentioning

confidence: 84%

Somatic, hematologic phenotype, long‐term outcome, and effect of hematopoietic stem cell transplantation. An analysis of 97 Fanconi anemia patients from the Italian national database on behalf of the Marrow Failure Study Group of the AIEOP (Italian Association of Pediatric Hematology–Oncology)

et al. 2016

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“…Reverse mosaicism was considered when chromosomal aberrations were observed in ,50% of the cells after diepoxybuthane treatment. 13 Studies were all performed under institutional review board-approved protocols by the involved research centers.…”

Section: Patient Cohort and Samplesmentioning

confidence: 99%

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

et al. 2017

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Key Points• Fanconi anemia patients have exacerbated cytogenetic clonal mosaicism as detected by molecular karyotyping of blood DNA with SNP assays.• Bone marrow clonal abnormalities can be detected in blood DNA and used as biomarkers of cancer risk and poor prognosis.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 ( ). 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.

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“…17 Classification of patients as having T-cell mosaicism was based on a percentage of aberrant cells less than 50% to 60%. 18 Family informed consent was obtained for all patients included in this study in accordance with the Declaration of Helsinki. This investigation was approved by the Universitat Autònoma de Barcelona University Ethical Committee on Human Research.…”

Section: Patients and Samplesmentioning

confidence: 99%

Origin, functional role, and clinical impact of Fanconi anemia FANCA mutations

Castellà

Pujol

Callén

et al. 2011

Blood

115

126

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Chromosome fragility in patients with Fanconi anaemia: diagnostic implications and clinical impact

Abstract: This study proposes a new chromosome fragility index and suggests that genome instability during embryo development may be related to malformations in FA, while DEB-induced chromosome breaks in T cells have no prognostic value for the haematological disease.

Cited by 52 publications

References 36 publications

Somatic, hematologic phenotype, long‐term outcome, and effect of hematopoietic stem cell transplantation. An analysis of 97 Fanconi anemia patients from the Italian national database on behalf of the Marrow Failure Study Group of the AIEOP (Italian Association of Pediatric Hematology–Oncology)

Somatic, hematologic phenotype, long‐term outcome, and effect of hematopoietic stem cell transplantation. An analysis of 97 Fanconi anemia patients from the Italian national database on behalf of the Marrow Failure Study Group of the AIEOP (Italian Association of Pediatric Hematology–Oncology)

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

Origin, functional role, and clinical impact of Fanconi anemia FANCA mutations

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