Complex chromosomal rearrangements leading to MECOM overexpression are recurrent in myeloid malignancies with various 3q abnormalities

Carmen Baldazzi, Simona Luatti, Elisa Zuffa, Cristina Papayannidis, Emanuela Ottaviani, Giulia Marzocchi, Gaia Ameli, Maria Antonella Bardi, Laura Bonaldi, Rossella Paolini, Carmela Gurrieri, Gian Matteo Rigolin, Antonio Cuneo, Giovanni Martinelli, Michele Cavo, Nicoletta Testoni

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Chromosomal rearrangements involving 3q26 are recurrent findings in myeloid malignancies leading to MECOM overexpression, which has been associated with a very poor prognosis. Other 3q abnormalities have been reported and cryptic MECOM rearrangements have been identified in some cases. By fluorescence in situ hybridization (FISH) analysis, we investigated 97 acute myeloid leukemia/myelodysplastic syndrome patients with various 3q abnormalities to determine the role and the frequency of the involvement of MECOM. We identified MECOM rearrangements in 51 patients, most of them showed 3q26 involvement by chromosome banding analysis (CBA): inv(3)/t(3;3) (n=26) and other balanced 3q26 translocations (t(3q26)) (n=15); the remaining cases (n=10) showed various 3q abnormalities: five with balanced translocations involving 3q21 or 3q25; two with homogenously staining region (hsr) on 3q; and three with other various 3q abnormalities. Complex rearrangements with multiple breakpoints on 3q, masking 3q26 involvement, were identified in cases with 3q21/3q25 translocations. Furthermore, multiple breaks were observed in two cases with t(3q26), suggesting that complex rearrangement may also occur in apparently simple t(3q26). Intrachromosomal gene amplification was another mechanism leading to MECOM overexpression in two cases with hsr on 3q. In the last three cases, FISH analysis revealed 3q26 involvement that was missed by CBA because of metaphases' suboptimal quality. All cases with MECOM rearrangements showed overexpression by real-time quantitative PCR. Finally, MECOM rearrangements can occur in patients with 3q abnormalities even in the absence of specific 3q26 involvement, underlining that their frequency is underestimated. As MECOM rearrangement has been associated with very poor prognosis, its screening should be performed in patients with any 3q abnormalities.

Original languageEnglish
Pages (from-to)375-388
Number of pages14
JournalGenes Chromosomes and Cancer
Volume55
Issue number4
DOIs
Publication statusPublished - Apr 1 2016

Fingerprint

Chromosome Banding
Fluorescence In Situ Hybridization
Neoplasms
Staining and Labeling
Gene Amplification
Myelodysplastic Syndromes
Metaphase
Acute Myeloid Leukemia
Real-Time Polymerase Chain Reaction

ASJC Scopus subject areas

  • Cancer Research
  • Genetics

Cite this

Complex chromosomal rearrangements leading to MECOM overexpression are recurrent in myeloid malignancies with various 3q abnormalities. / Baldazzi, Carmen; Luatti, Simona; Zuffa, Elisa; Papayannidis, Cristina; Ottaviani, Emanuela; Marzocchi, Giulia; Ameli, Gaia; Bardi, Maria Antonella; Bonaldi, Laura; Paolini, Rossella; Gurrieri, Carmela; Rigolin, Gian Matteo; Cuneo, Antonio; Martinelli, Giovanni; Cavo, Michele; Testoni, Nicoletta.

In: Genes Chromosomes and Cancer, Vol. 55, No. 4, 01.04.2016, p. 375-388.

Research output: Contribution to journalArticle

Baldazzi, C, Luatti, S, Zuffa, E, Papayannidis, C, Ottaviani, E, Marzocchi, G, Ameli, G, Bardi, MA, Bonaldi, L, Paolini, R, Gurrieri, C, Rigolin, GM, Cuneo, A, Martinelli, G, Cavo, M & Testoni, N 2016, 'Complex chromosomal rearrangements leading to MECOM overexpression are recurrent in myeloid malignancies with various 3q abnormalities', Genes Chromosomes and Cancer, vol. 55, no. 4, pp. 375-388. https://doi.org/10.1002/gcc.22341
Baldazzi, Carmen ; Luatti, Simona ; Zuffa, Elisa ; Papayannidis, Cristina ; Ottaviani, Emanuela ; Marzocchi, Giulia ; Ameli, Gaia ; Bardi, Maria Antonella ; Bonaldi, Laura ; Paolini, Rossella ; Gurrieri, Carmela ; Rigolin, Gian Matteo ; Cuneo, Antonio ; Martinelli, Giovanni ; Cavo, Michele ; Testoni, Nicoletta. / Complex chromosomal rearrangements leading to MECOM overexpression are recurrent in myeloid malignancies with various 3q abnormalities. In: Genes Chromosomes and Cancer. 2016 ; Vol. 55, No. 4. pp. 375-388.
@article{9fe86d19edea456f9eaae0622775bbb7,
title = "Complex chromosomal rearrangements leading to MECOM overexpression are recurrent in myeloid malignancies with various 3q abnormalities",
abstract = "Chromosomal rearrangements involving 3q26 are recurrent findings in myeloid malignancies leading to MECOM overexpression, which has been associated with a very poor prognosis. Other 3q abnormalities have been reported and cryptic MECOM rearrangements have been identified in some cases. By fluorescence in situ hybridization (FISH) analysis, we investigated 97 acute myeloid leukemia/myelodysplastic syndrome patients with various 3q abnormalities to determine the role and the frequency of the involvement of MECOM. We identified MECOM rearrangements in 51 patients, most of them showed 3q26 involvement by chromosome banding analysis (CBA): inv(3)/t(3;3) (n=26) and other balanced 3q26 translocations (t(3q26)) (n=15); the remaining cases (n=10) showed various 3q abnormalities: five with balanced translocations involving 3q21 or 3q25; two with homogenously staining region (hsr) on 3q; and three with other various 3q abnormalities. Complex rearrangements with multiple breakpoints on 3q, masking 3q26 involvement, were identified in cases with 3q21/3q25 translocations. Furthermore, multiple breaks were observed in two cases with t(3q26), suggesting that complex rearrangement may also occur in apparently simple t(3q26). Intrachromosomal gene amplification was another mechanism leading to MECOM overexpression in two cases with hsr on 3q. In the last three cases, FISH analysis revealed 3q26 involvement that was missed by CBA because of metaphases' suboptimal quality. All cases with MECOM rearrangements showed overexpression by real-time quantitative PCR. Finally, MECOM rearrangements can occur in patients with 3q abnormalities even in the absence of specific 3q26 involvement, underlining that their frequency is underestimated. As MECOM rearrangement has been associated with very poor prognosis, its screening should be performed in patients with any 3q abnormalities.",
author = "Carmen Baldazzi and Simona Luatti and Elisa Zuffa and Cristina Papayannidis and Emanuela Ottaviani and Giulia Marzocchi and Gaia Ameli and Bardi, {Maria Antonella} and Laura Bonaldi and Rossella Paolini and Carmela Gurrieri and Rigolin, {Gian Matteo} and Antonio Cuneo and Giovanni Martinelli and Michele Cavo and Nicoletta Testoni",
year = "2016",
month = "4",
day = "1",
doi = "10.1002/gcc.22341",
language = "English",
volume = "55",
pages = "375--388",
journal = "Genes Chromosomes and Cancer",
issn = "1045-2257",
publisher = "Wiley-Liss Inc.",
number = "4",

}

TY - JOUR

T1 - Complex chromosomal rearrangements leading to MECOM overexpression are recurrent in myeloid malignancies with various 3q abnormalities

AU - Baldazzi, Carmen

AU - Luatti, Simona

AU - Zuffa, Elisa

AU - Papayannidis, Cristina

AU - Ottaviani, Emanuela

AU - Marzocchi, Giulia

AU - Ameli, Gaia

AU - Bardi, Maria Antonella

AU - Bonaldi, Laura

AU - Paolini, Rossella

AU - Gurrieri, Carmela

AU - Rigolin, Gian Matteo

AU - Cuneo, Antonio

AU - Martinelli, Giovanni

AU - Cavo, Michele

AU - Testoni, Nicoletta

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Chromosomal rearrangements involving 3q26 are recurrent findings in myeloid malignancies leading to MECOM overexpression, which has been associated with a very poor prognosis. Other 3q abnormalities have been reported and cryptic MECOM rearrangements have been identified in some cases. By fluorescence in situ hybridization (FISH) analysis, we investigated 97 acute myeloid leukemia/myelodysplastic syndrome patients with various 3q abnormalities to determine the role and the frequency of the involvement of MECOM. We identified MECOM rearrangements in 51 patients, most of them showed 3q26 involvement by chromosome banding analysis (CBA): inv(3)/t(3;3) (n=26) and other balanced 3q26 translocations (t(3q26)) (n=15); the remaining cases (n=10) showed various 3q abnormalities: five with balanced translocations involving 3q21 or 3q25; two with homogenously staining region (hsr) on 3q; and three with other various 3q abnormalities. Complex rearrangements with multiple breakpoints on 3q, masking 3q26 involvement, were identified in cases with 3q21/3q25 translocations. Furthermore, multiple breaks were observed in two cases with t(3q26), suggesting that complex rearrangement may also occur in apparently simple t(3q26). Intrachromosomal gene amplification was another mechanism leading to MECOM overexpression in two cases with hsr on 3q. In the last three cases, FISH analysis revealed 3q26 involvement that was missed by CBA because of metaphases' suboptimal quality. All cases with MECOM rearrangements showed overexpression by real-time quantitative PCR. Finally, MECOM rearrangements can occur in patients with 3q abnormalities even in the absence of specific 3q26 involvement, underlining that their frequency is underestimated. As MECOM rearrangement has been associated with very poor prognosis, its screening should be performed in patients with any 3q abnormalities.

AB - Chromosomal rearrangements involving 3q26 are recurrent findings in myeloid malignancies leading to MECOM overexpression, which has been associated with a very poor prognosis. Other 3q abnormalities have been reported and cryptic MECOM rearrangements have been identified in some cases. By fluorescence in situ hybridization (FISH) analysis, we investigated 97 acute myeloid leukemia/myelodysplastic syndrome patients with various 3q abnormalities to determine the role and the frequency of the involvement of MECOM. We identified MECOM rearrangements in 51 patients, most of them showed 3q26 involvement by chromosome banding analysis (CBA): inv(3)/t(3;3) (n=26) and other balanced 3q26 translocations (t(3q26)) (n=15); the remaining cases (n=10) showed various 3q abnormalities: five with balanced translocations involving 3q21 or 3q25; two with homogenously staining region (hsr) on 3q; and three with other various 3q abnormalities. Complex rearrangements with multiple breakpoints on 3q, masking 3q26 involvement, were identified in cases with 3q21/3q25 translocations. Furthermore, multiple breaks were observed in two cases with t(3q26), suggesting that complex rearrangement may also occur in apparently simple t(3q26). Intrachromosomal gene amplification was another mechanism leading to MECOM overexpression in two cases with hsr on 3q. In the last three cases, FISH analysis revealed 3q26 involvement that was missed by CBA because of metaphases' suboptimal quality. All cases with MECOM rearrangements showed overexpression by real-time quantitative PCR. Finally, MECOM rearrangements can occur in patients with 3q abnormalities even in the absence of specific 3q26 involvement, underlining that their frequency is underestimated. As MECOM rearrangement has been associated with very poor prognosis, its screening should be performed in patients with any 3q abnormalities.

UR - http://www.scopus.com/inward/record.url?scp=84958768838&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84958768838&partnerID=8YFLogxK

U2 - 10.1002/gcc.22341

DO - 10.1002/gcc.22341

M3 - Article

C2 - 26815134

AN - SCOPUS:84958768838

VL - 55

SP - 375

EP - 388

JO - Genes Chromosomes and Cancer

JF - Genes Chromosomes and Cancer

SN - 1045-2257

IS - 4

ER -