Cytogenetics in Fanconi Anemia: The Importance of Follow-Up and the Search for New Biomarkers of Genomic Instability

Fanconi Anemia (FA) is a disease characterized by genomic instability, increased sensitivity to DNA cross-linking agents, and the presence of clonal chromosomal abnormalities. This genomic instability can compromise the bone marrow (BM) and confer a high cancer risk to the patients, particularly in the development of Myelodysplastic Syndrome (MDS) and Acute Myeloid Leukemia (AML). The diagnosis of FA patients is complex and cannot be based only on clinical features at presentation. The gold standard diagnostic assay for these patients is cytogenetic analysis, revealing chromosomal breaks induced by DNA cross-linking agents. Clonal chromosome abnormalities, such as the ones involving chromosomes 1q, 3q, and 7, are also common features in FA patients and are associated with progressive BM failure and/or a pre-leukemia condition. In this review, we discuss the cytogenetic methods and their application in diagnosis, stratification of the patients into distinct prognostic groups, and the clinical follow-up of FA patients. These methods have been invaluable for the understanding of FA pathogenesis and identifying novel disease biomarkers. Additional evidence is required to determine the association of these biomarkers with prognosis and cancer risk, and their potential as druggable targets for FA therapy

Cytogenetic study of Brazilian patients with myelodysplastic syndrome (MDS)

Bone marrow cytogenetic studies were performed on 93 patients with primary myelodysplastic syndrome (MDS) diagnosed at the Clinical Hospital of the Federal University of Paraná, Brazil. Chromosomal alterations were observed in 69% of the patients. Monosomy of chromosome 7, deletions of 7q, 5q, 12p and 20q, rearrangements of 11q23 and trisomies of chromosomes 8 and 21 were the most frequent abnormalities observed. Among adult patients the most frequent aberrations were rearrangements of 11q23 and 12p deletions. In the pediatric group, 5q deletions and monosomy of chromosome 7 were the most common alterations