Deciphering the complexities of MECOM rearrangement-driven chromosomal aberrations

Abstract

MECOM rearrangement is associated with rapid disease progression and poor prognosis in myeloid neoplasms. Previous studies were often based on 3q26.2 abnormalities without confirmation of MECOM status. The frequency of MECOM rearrangement and attribution of various chromosomal aberrations remain poorly characterized. This study presented 129 cases with confirmed MECOM rearrangement by karyotyping and multiple FISH methodologies. MECOM rearrangement arose through translocation (49.6%, n = 64), inversion (40.3%, n = 52), insertion (5.4%, n = 7) or unknown mechanism(s) (4.7%, n = 6). The classic inv(3)(q21q26.2) was dominant (n = 50) in inversion-driven MECOM rearrangement; and 3 of them also had double inv(3). For translocation-driven MECOM rearrangement, t(3;21) was most common (n = 15), followed by t(2;3) (n = 13), t(3;12) (n = 10), t(3;3) (n = 9), t(3;8) (n = 6), t(3;6) and t(3;17) (n = 4 each), t(1;3) and t(3;?) (n = 1 each). Cases with t(3;3)-, t(3;12)-, and insertion-driven MECOM rearrangement were prone to exhibit a complex karyotype, while cases with t(2;3)-, t(3;21)- and insertion-driven MECOM rearrangement were prone to have an "unbalanced" MECOM FISH signal pattern, likely caused by uncommon breakpoint(s) within the target of 5'MECOM probe. Therefore, atypical chromosomal aberrations and/or mechanisms are involved in MECOM rearrangement. Confirmation/exclusion of MECOM rearrangement is necessary in all cases with a 3q26.2 abnormality. (Word count: 190).

Keywords: Fluorescence in situ hybridization (FISH); Karyotyping; MECOM rearrangement; Map-back; Myeloid neoplasms; aCGH.