title: Clonal chromosomal aberrations in bone marrow cells of Fanconi anemia patients: gains of the chromosomal segment 3q26q29 as an adverse risk factor.
abstract: Fanconi anemia (FA) is a condition that induces susceptibility to bone marrow failure, myelodysplastic syndrome (MDS), and leukemia. We report on a high incidence of expanding clonal aberrations with partial trisomies and tetrasomies of chromosome 3q in bone marrow cells of 18 of 53 FA patients analyzed, detected by conventional and molecular cytogenetics. To determine the clinical relevance of these findings, we compared the cytogenetic data, the morphologic features of the bone marrow, and the clinical course of these patients with those of 35 FA patients without clonal aberrations of 3q. The 2 groups did not differ significantly with respect to age, sex, or complementation group. There was a significant survival advantage of patients without abnormalities of chromosome 3q. Even more pronounced was the risk assessment of patients with gains of 3q material with respect to the development of morphologic MDS and acute myeloid leukemia (AML). Thus, our data from 18 patients with 3q aberrations reveal that gains of 3q are strongly associated with a poor prognosis and represent an adverse risk factor in FA.
authors.affiliation: Institute of Human Genetics, Charité, Campus-Virchow, Humboldt-University, Berlin, Germany.
authors.forename: Holger
authors.initials: H
authors.lastname: Tönnies
authors.forename: Stefanie
authors.initials: S
authors.lastname: Huber
authors.forename: Jörn-Sven
authors.initials: JS
authors.lastname: Kuhl
authors.forename: Antje
authors.initials: A
authors.lastname: Gerlach
authors.forename: Wolfram
authors.initials: W
authors.lastname: Ebell
authors.forename: Heidemarie
authors.initials: H
authors.lastname: Neitzel
mesh_terms: D000328:Adult; D001853:Bone Marrow / Q000473:pathology; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002893:Chromosomes, Human, Pair 3; D005199:Fanconi Anemia / Q000235:genetics* / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D015470:Leukemia, Myeloid, Acute / Q000453:epidemiology* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000453:epidemiology* / Q000235:genetics; D012307:Risk Factors