title: Genomic gain at 6p21: a new cryptic molecular rearrangement in secondary myelodysplastic syndrome and acute myeloid leukemia.
abstract: Fluorescence in situ hybridization and comparative genomic hybridization characterized 6p rearrangements in eight primary and in 10 secondary myeloid disorders (including one patient with Fanconi anemia) and found different molecular lesions in each group. In primary disorders, 6p abnormalities, isolated in six patients, were highly heterogeneous with different breakpoints along the 6p arm. Reciprocal translocations were found in seven. In the 10 patients with secondary acute myeloid leukemia/myelodysplastic syndrome (AML/MDS), the short arm of chromosome 6 was involved in unbalanced translocations in 7. The other three patients showed full or partial trisomy of the 6p arm, that is, i(6)(p10) (one patient) and dup(6)(p) (two patients). In 5/7 patients with unbalanced translocations, DNA sequences were overrepresented at band 6p21 as either cryptic duplications (three patients) or cryptic low-copy gains (two patients). In the eight patients with cytogenetic or cryptic 6p gains, we identified a common overrepresented region extending for 5-6 megabases from the TNF gene to the ETV-7 gene. 6p abnormalities were isolated karyotype changes in four patients. Consequently, in secondary AML/MDS, we hypothesize that 6p gains are major pathogenetic events arising from acquired and/or congenital genomic instability.
authors.affiliation: Hematology and Bone Marrow Transplantation Unit, University of Perugia, Perugia, Italy.
authors.forename: R
authors.initials: R
authors.lastname: La Starza
authors.forename: A
authors.initials: A
authors.lastname: Aventin
authors.forename: C
authors.initials: C
authors.lastname: Matteucci
authors.forename: B
authors.initials: B
authors.lastname: Crescenzi
authors.forename: S
authors.initials: S
authors.lastname: Romoli
authors.forename: N
authors.initials: N
authors.lastname: Testoni
authors.forename: V
authors.initials: V
authors.lastname: Pierini
authors.forename: S
authors.initials: S
authors.lastname: Ciolli
authors.forename: C
authors.initials: C
authors.lastname: Sambani
authors.forename: A
authors.initials: A
authors.lastname: Locasciulli
authors.forename: E
authors.initials: E
authors.lastname: Di Bona
authors.forename: M
authors.initials: M
authors.lastname: Lafage-Pochitaloff
authors.forename: M F
authors.initials: MF
authors.lastname: Martelli
authors.forename: P
authors.initials: P
authors.lastname: Marynen
authors.forename: C
authors.initials: C
authors.lastname: Mecucci
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics*; D020732:Cytogenetic Analysis; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007951:Leukemia, Myeloid / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics*; D016609:Neoplasms, Second Primary / Q000175:diagnosis / Q000235:genetics*; D012680:Sensitivity and Specificity; D014178:Translocation, Genetic / Q000235:genetics*