Heterogeneity of genomic breakpoints in MSN-ALK translocations in anaplastic large cell lymphoma.
Anaplastic large cell lymphomas (ALCL) are associated with the t(2;5)(p23;q35) translocation involving the anaplastic lymphoma kinase (ALK) and the nucleophosmin (NPM) genes. However, genes other than NPM may fuse to ALK in these tumors. In this study we have identified an ALCL with a distinctive cell membrane-restrictive ALK immunostaining in which the molecular characterization showed a new fusion gene between moesin (MSN) and ALK with different breakpoints than previously recognized. The ALK breakpoint occurred in an exonic sequence, and the chimeric gene included an intronic sequence of MSN. Identification of the genomic breakpoint in the derivative chromosome 2 revealed a 72-base pair deletion involving both MSN and ALK sequences. These findings provide further evidence of the breakpoint heterogeneity in ALK translocations and highlight the importance of ALK immunostaining in the diagnosis of ALCL and the identification of the underlying genetic abnormalities in this lymphoma.
Laboratory of Pathology, Hospital Clinic, Institut d'Investigacions Biomèdiques August Pi i Sunyer, University of Barcelona, Spain.
Frederic
F
Tort
Elias
E
Campo
Brad
B
Pohlman
Eric
E
Hsi
D000328:Adult; D000077548:Anaplastic Lymphoma Kinase; D000971:Antineoplastic Combined Chemotherapy Protocols; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000378:metabolism; D004273:DNA, Neoplasm / Q000032:analysis; D017809:Fatal Outcome; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016130:Immunophenotyping; D016403:Lymphoma, Large B-Cell, Diffuse / Q000201:enzymology* / Q000235:genetics* / Q000473:pathology; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009367:Neoplasm Staging; D016133:Polymerase Chain Reaction; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020794:Receptor Protein-Tyrosine Kinases; D014178:Translocation, Genetic
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; D008840:Microfilament Proteins; D012333:RNA, Messenger; C071058:moesin; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases