title: Clinical and biologic implications of recurrent genomic aberrations in myeloma.
abstract: Nonrandom recurrent chromosomal abnormalities are ubiquitous in multiple myeloma (MM) and include, among others, translocations of the immunoglobulin heavy chain locus (IgH). IgH translocations in MM result in the up-regulation of oncogenes, and include more commonly t(11;14)(q13;q32), t(4;14)(p16;q32), and t(14;16)(q32;q23). Based on the recurrent nature of these translocations and their finding since the early stages of the plasma cell (PC) disorders, we hypothesized that they would confer biologic and clinical variability. In addition, deletions of 13q14 and 17p13 have also been associated with a shortened survival. We used cytoplasmic Ig-enhanced interphase fluorescent in situ hybridization to detect deletions (13q14 and 17p13.1), and translocations involving IgH in 351 patients treated with conventional chemotherapy entered into the Eastern Cooperative Oncology Group clinical trial E9486/9487. Translocations were frequently unbalanced with loss of one of the derivative chromosomes. The presence of t(4; 14)(p16;q32) (n = 42; 26 vs 45 months, P <.001), t(14;16)(q32;q23) (n = 15; 16 vs 41 months, P =.003), - 17p13 (n = 37; 23 vs 44 months, P =.005), and - 13q14 (n = 176; 35 vs 51 months, P =.028) were associated with shorter survival. A stratification of patients into 3 distinct categories allowed for prognostication: poor prognosis group (t(4;14)(p16;q32), t(14; 16)(q32;q23), and - 17p13), intermediate prognosis (- 13q14), and good prognosis group (all others), with median survivals of 24.7, 42.3, and 50.5 months, respectively (P <.001). This molecular cytogenetic classification identifies patients into poor, intermediate, and good risk categories. More importantly it provides further compelling evidence that MM is composed of subgroups of patients categorized according to their underlying genomic aberrations.
authors.affiliation: Mayo Cinic Division of Hematology, Department of laboratory Medicine, Rochester, MN 55905, USA. fonseca.rafael@mayo.edu
authors.forename: Rafael
authors.initials: R
authors.lastname: Fonseca
authors.forename: Emily
authors.initials: E
authors.lastname: Blood
authors.forename: Montserrat
authors.initials: M
authors.lastname: Rue
authors.forename: David
authors.initials: D
authors.lastname: Harrington
authors.forename: Martin M
authors.initials: MM
authors.lastname: Oken
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kyle
authors.forename: Gordon W
authors.initials: GW
authors.lastname: Dewald
authors.forename: Brian
authors.initials: B
authors.lastname: Van Ness
authors.forename: Scott A
authors.initials: SA
authors.lastname: Van Wier
authors.forename: Kimberly J
authors.initials: KJ
authors.lastname: Henderson
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Bailey
authors.forename: Philip R
authors.initials: PR
authors.lastname: Greipp
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D012008:Recurrence; D016019:Survival Analysis; D014178:Translocation, Genetic
chemical_list: D007143:Immunoglobulin Heavy Chains