title: Frequency of del(12p) is commonly underestimated in myelodysplastic syndromes: Results from a German diagnostic study in comparison with an international control group.
abstract: In myelodysplastic syndromes (MDS), deletion of the short arm of chromosome 12 (del(12p)) is usually a small abnormality, rarely detected as a single aberration by chromosome banding analysis (CBA) of bone marrow metaphases. Del(12p) has been described in 0.6 to 5% of MDS patients at initial diagnosis and is associated with a good to intermediate prognosis as a sole anomaly according to current scoring systems. Here, we present the results of a systematic del(12p) testing in a German prospective diagnostic study (clinicaltrials.gov: NCT01355913) on 367 MDS patients in whom CD34+ peripheral blood cells were analysed for the presence of del(12p) by sequential fluorescence in situ hybridization (FISH) analyses. A cohort of 2,902 previously published MDS patients diagnosed by CBA served as control. We demonstrate that, using a sensitive FISH technique, 12p deletion occurs significantly more frequently in MDS than previously described (7.6% by CD34+ PB-FISH vs. 1.6% by CBA, P < 0.001) and is often associated with other aberrations (93% by CD34+ PB-FISH vs. 60% by CBA). Additionally, the detection rate can be increased by repeated analyses in a patient over time which is important for the patient´s prognosis to distinguish a sole anomaly from double or complex aberrations. To our knowledge, this is the first study to screen for 12p deletions with a suitable probe for ETV6/TEL in 12p13. Our data suggest that the supplement of a probe for the detection of a 12p deletion to common FISH probe panels helps to avoid missing a del(12p), especially as part of more complex aberrations.
authors.affiliation: Department of Hematology and Medical Oncology, University Medicine of Goettingen, Germany.
authors.forename: Friederike
authors.initials: F
authors.lastname: Braulke
authors.affiliation: Department of Hematology and Oncology, Technical University of Munich, Germany.
authors.forename: Catharina
authors.initials: C
authors.lastname: Müller-Thomas
authors.affiliation: Department of Hematology and Oncology, Technical University of Munich, Germany.
authors.forename: Katharina
authors.initials: K
authors.lastname: Götze
authors.affiliation: Department of Hematology and Oncology, University of Dresden, Germany.
authors.forename: Uwe
authors.initials: U
authors.lastname: Platzbecker
authors.affiliation: Department of Hematology and Oncology, University of Duesseldorf, Germany.
authors.forename: Ulrich
authors.initials: U
authors.lastname: Germing
authors.affiliation: Department of Hematology and Oncology, University Hospital of Mannheim, Germany.
authors.forename: Wolf-Karsten
authors.initials: WK
authors.lastname: Hofmann
authors.affiliation: Department of Hematology and Oncology, Marienhospital, Duesseldorf, Germany.
authors.forename: Aristoteles A N
authors.initials: AA
authors.lastname: Giagounidis
authors.affiliation: Department of Hematology and Oncology, University of Freiburg Medical Center, Freiburg, Germany.
authors.forename: Michael
authors.initials: M
authors.lastname: Lübbert
authors.affiliation: Department of Hematology, Stanford University Cancer Center, Stanford, CA.
authors.forename: Peter L
authors.initials: PL
authors.lastname: Greenberg
authors.affiliation: University of Rochester Medical Center, Rochester, NY.
authors.forename: John M
authors.initials: JM
authors.lastname: Bennett
authors.affiliation: Institut De Recerca Contra La Leukemia Josep Carreras, Badalona, Spain.
authors.forename: Francesc
authors.initials: F
authors.lastname: Solé
authors.affiliation: Sonora Quest Laboratories, Phoenix, AZ.
authors.forename: Marilyn L
authors.initials: ML
authors.lastname: Slovak
authors.affiliation: Tokyo Medical University, Tokyo, Japan.
authors.forename: Kazuma
authors.initials: K
authors.lastname: Ohyashiki
authors.affiliation: Section of Hematology and Oncology, University of Chicago, Chicago, IL.
authors.forename: Michelle M
authors.initials: MM
authors.lastname: Le Beau
authors.affiliation: Hanusch Hospital Boltzmann Institute for Leukemia Research, Vienna, Austria.
authors.forename: Heinz
authors.initials: H
authors.lastname: Tüchler
authors.affiliation: Third Medical Department for Hematology and Oncology and L. Boltzmann Cluster Oncology, Hanusch Hospital, Vienna, Austria.
authors.forename: Michael
authors.initials: M
authors.lastname: Pfeilstöcker
authors.affiliation: Department of Human Genetics, University of Düsseldorf, Düsseldorf, Germany.
authors.forename: Barbara
authors.initials: B
authors.lastname: Hildebrandt
authors.affiliation: Department of Hematology, Oncology and Clinical Immunology, St. Johannes Hospital, Duisburg, Germany.
authors.forename: Carlo
authors.initials: C
authors.lastname: Aul
authors.affiliation: Department of Internal Medicine, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Reinhard
authors.initials: R
authors.lastname: Stauder
authors.affiliation: Department of Internal Medicine I, Division of Hematology and Hemostaseology and Ludwig Boltzmann Cluster Oncology, Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Valent
authors.affiliation: Department of Medical Genetics, Medical University of Vienna, Vienna, Austria.
authors.forename: Christa
authors.initials: C
authors.lastname: Fonatsch
authors.affiliation: Department of Hematology and Medical Oncology, University Medicine of Goettingen, Germany.
authors.forename: Ulrike
authors.initials: U
authors.lastname: Bacher
authors.affiliation: Department of Hematology and Medical Oncology, University Medicine of Goettingen, Germany.
authors.forename: Lorenz
authors.initials: L
authors.lastname: Trümper
authors.affiliation: Department of Hematology and Medical Oncology, University Medicine of Goettingen, Germany.
authors.forename: Detlef
authors.initials: D
authors.lastname: Haase
authors.affiliation: Department of Hematology and Medical Oncology, University Medicine of Goettingen, Germany.
authors.forename: Julie
authors.initials: J
authors.lastname: Schanz
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D018952:Antigens, CD34 / Q000235:genetics; D002871:Chromosome Banding; D002872:Chromosome Deletion; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D035061:Control Groups; D005260:Female; D005858:Germany; D006801:Humans; D017404:In Situ Hybridization, Fluorescence / Q000379:methods*; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D011379:Prognosis; D011446:Prospective Studies; D050783:Proto-Oncogene Proteins c-ets / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics; D055815:Young Adult; D000097764:ETS Translocation Variant 6 Protein
chemical_list: D018952:Antigens, CD34; D050783:Proto-Oncogene Proteins c-ets; D012097:Repressor Proteins; D000097764:ETS Translocation Variant 6 Protein