Assessment of t(2;5)(p23;q35) translocation and variants in pediatric ALK+ anaplastic large cell lymphoma.
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.
Liang
Xiayuan
X
Department of Pathology, University of Colorado School of Medicine, Denver, USA.
Meech
Sandra J
SJ
Odom
Lorrie F
LF
Bitter
Mitchell A
MA
Ryder
John W
JW
Hunger
Stephen P
SP
Lovell
Mark A
MA
Meltesen
Lynn
L
Wei
Qi
Q
Williams
Sara A
SA
Hutchinson
Rebecca N
RN
McGavran
Loris
L
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
C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases