Searching for Amplification of Chromosome 5 Segments by Molecular Cytogenetics in 9 Myelodysplastic Syndromes/Acute Myeloid Leukemia (MDS)/(AML) Patients with Apparent Monosomy 5
Authors: Bernasconi Paolo , Dambruoso Irene , Boni Marina , Zappatore Rita , Cavigliano Paola Maria , Giardini Ilaria , Caresa Marilena , Astori Cesare , Castagnola Carlo , Lazzarino Mario 
Published: April 2020

Abstract
Based on conventional cytogenetic studies, acquired losses of the whole or a part of chromosome 5, alone or in a complex karyotype (defined by the presence of ≥3 chromosome defects), are recurrent cyogenetic defects in MDS and AML. The size of the deleted material and the breakpoints vary among patients. Commonly deleted regions are bands 5q13, 5q31-q32, and 5q33-q34-q35. Monosomy 5 (−5), too, has always been considered a non-random chromosomal defect. However, recent evidence is changing this assumption since most patients with −5 on CC studies present a chromosome 5 fragmentation in more than two segments on FISH investigations (Herry et al, 2007). The present FISH study was aimed at establishing the incidence of true −5 and at refining chromosome 5 abnormalities in 9 patients, one MDS, classified as refractory anemia with excess of blasts type 1 and 8 AML (2 M2, 5 M4 and one M5). Monosomy 5 was the only karyotype defect in 2 patients and part of a complex karyotype in the remaining 7. CC and FISH studies were performed as already reported (Bernasconi et al, 2007). FISH analyses were carried out on mitotic figures with the following probes: the LSI CSF1R/D5S721:D5S23, mapped at 5q33 (spectrum orange) and 5p (spectrum green) from Vysis (Abbott Molecular/Vysis, North Chicago, IL, USA) and the WCP5SO probes from QBiogene (Qbiogene Inc., Carslbad, CA, USA). Additional FISH investigations were carried out with two BAC probes exploring the 5q segment comprised between the centromere and band 5q11 in order to check whether this chromosomal region was either maintained or deleted. The WCP5SO probe demonstrated that all the 9 patients presented an apparent monosomy 5 since chromosome 5 material was contained within marker chromosomes already identified by CC. In 3 patients the LSI CSF1R/D5S721:D5S23 probe provided three green signals (5p duplication) along with one red signal (5q33 monosomy). In these patients one green/red signals were mapped on the normal chromosome 5, the other two green signals were localized on marker chromosomes. In the remaining 6 patients the same probe demonstrated one green/red signal on the normal chromosome 5 and another green signal on a marker chromosome. Subsequently all the 9 patients were investigated with the 5q11 BAC probes. Five patients showed two signals revealing that band 5q11 was maintained. Considering the 4 patients with loss of band 5q11, 3 presented a fragmentation of chromosome 5 and one an internal chromosome 5 rearrangement. In conclusion our data show that true monosomy 5 is a very uncommon event in MDS/AML since in all our patients with −5 on CC 5p was either maintained or amplified. In addition, band 5q11 was maintained in 5/9 patients. In view of these results our future goal will be to check whether other 5q regions are maintained or deleted in these complex chromosome 5 rearrangements.