Braulke Friederike, Müller-Thomas Catharina, Götze Katharina, Platzbecker Uwe, Germing Ulrich, Hofmann Wolf-Karsten, Giagounidis Aristoteles A N, Lübbert Michael, Greenberg Peter L, Bennett John M, Solé Francesc, Slovak Marilyn L, Ohyashiki Kazuma, Le Beau Michelle M, Tüchler Heinz, Pfeilstöcker Michael, Hildebrandt Barbara, Aul Carlo, Stauder Reinhard, Valent Peter, Fonatsch Christa, Bacher Ulrike, Trümper Lorenz, Haase Detlef, Schanz Julie
Department of Hematology and Medical Oncology, University Medicine of Goettingen, Germany.
Department of Hematology and Oncology, Technical University of Munich, Germany.
Genes Chromosomes Cancer. 2015 Dec;54(12):809-17. doi: 10.1002/gcc.22292. Epub 2015 Sep 10.
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.
在骨髓增生异常综合征（MDS）中，12号染色体短臂缺失（del(12p)）通常是一种微小异常，在骨髓中期染色体显带分析（CBA）中很少作为单一畸变被检测到。在MDS患者初诊时，del(12p)的检出率为0.6%至5%，根据目前的评分系统，作为唯一异常时其预后良好至中等。在此，我们展示了在一项针对367例MDS患者的德国前瞻性诊断研究（clinicaltrials.gov：NCT01355913）中进行系统性del(12p)检测的结果，该研究通过序贯荧光原位杂交（FISH）分析检测CD34⁺外周血细胞中del(12p)的存在。一组2902例先前通过CBA诊断的MDS患者作为对照。我们证明，使用敏感的FISH技术，MDS中12p缺失的发生率明显高于先前描述的情况（CD34⁺外周血FISH检测为7.6%，而CBA检测为1.6%，P < 0.001），并且常与其他畸变相关（CD34⁺外周血FISH检测为93%，而CBA检测为60%）。此外，随着时间对患者进行重复分析可提高检出率，这对于区分单一异常与双重或复杂畸变对患者预后的判断很重要。据我们所知，这是第一项使用适合12p13中ETV6/TEL检测的探针筛查12p缺失的研究。我们的数据表明，在常用的FISH探针组合中补充用于检测12p缺失的探针有助于避免漏诊del(12p)，尤其是作为更复杂畸变的一部分时。
