title: Assessment of t(2;5)(p23;q35) translocation and variants in pediatric ALK+ anaplastic large cell lymphoma.
abstract: To evaluate t(2;5) and its variants, we studied 21 pediatric cases of anaplastic lymphoma kinase (ALK)+ anaplastic large cell lymphoma (ALCL) by using immunohistochemical staining, fluorescence in situ hybridization, cytogenetics, and reverse transcriptase-polymerase chain reaction. Results showed 7 (33%) cases with t(2;5), 6 (29%) with variant gene rearrangements, 7 (33%) with uncharacterized rearrangements, and 1 with ALK protein expression but no ALK rearrangement. Among 6 variant gene rearrangements, 1 had TPM4-ALK/t(2;19)(p23;p13) and 2 had inv(2) with the breakpoint proximate to ATIC-ALK and an unknown partner gene separately. The genetic features of the remaining 3 cases were as follows: ins(8;2) with an unknown partner gene; conversion from ALK- at diagnosis to ALK+ at recurrence with unspecified gene rearrangement; complex karyotype without involvement of 2p23, suggesting a cryptic translocation. Concordance between different laboratory results varied from 47% to 81%. These data suggest that ALK variants are not uncommon and underscore the necessity of integrating immunohistochemical, cytogenetic, and molecular genetic approaches to detect, characterize, and confirm t(2;5) and its variant translocations.
authors.affiliation: Department of Pathology, University of Colorado School of Medicine, Denver, USA.
authors.forename: Xiayuan
authors.initials: X
authors.lastname: Liang
authors.forename: Sandra J
authors.initials: SJ
authors.lastname: Meech
authors.forename: Lorrie F
authors.initials: LF
authors.lastname: Odom
authors.forename: Mitchell A
authors.initials: MA
authors.lastname: Bitter
authors.forename: John W
authors.initials: JW
authors.lastname: Ryder
authors.forename: Stephen P
authors.initials: SP
authors.lastname: Hunger
authors.forename: Mark A
authors.initials: MA
authors.lastname: Lovell
authors.forename: Lynn
authors.initials: L
authors.lastname: Meltesen
authors.forename: Qi
authors.initials: Q
authors.lastname: Wei
authors.forename: Sara A
authors.initials: SA
authors.lastname: Williams
authors.forename: Rebecca N
authors.initials: RN
authors.lastname: Hutchinson
authors.forename: Loris
authors.initials: L
authors.lastname: McGavran
mesh_terms: D000293:Adolescent; D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D005260:Female; D015321:Gene Rearrangement / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D016130:Immunophenotyping; D017404:In Situ Hybridization, Fluorescence; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics* / Q000378:metabolism*; D008297:Male; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases; D015203:Reproducibility of Results; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014178:Translocation, Genetic
chemical_list: C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases