title: Gene-expression profiling of systemic anaplastic large-cell lymphoma reveals differences based on ALK status and two distinct morphologic ALK+ subtypes.
abstract: With the use of microarray gene-expression profiling, we analyzed a homogeneous series of 32 patients with systemic anaplastic large-cell lymphoma (ALCL) and 5 ALCL cell lines. Unsupervised analysis classified ALCL in 2 clusters, corresponding essentially to morphologic subgroups (ie, common type vs small cell and "mixed" variants) and clinical variables. Patients with a morphologic variant of ALCL had advanced-stage disease. This group included a significant number of patients who experienced early relapse. Supervised analysis showed that ALK+ALCL and ALK- ALCL have different gene-expression profiles, further confirming that they are different entities. Among the most significantly differentially expressed genes between ALK+ and ALK- samples, we found BCL6, PTPN12, CEBPB, and SERPINA1 genes to be overexpressed in ALK+ ALCL. This result was confirmed at the protein level for BCL-6, C/EBPbeta and serpinA1 through tissue microarrays. The molecular signature of ALK- ALCL included overexpression of CCR7, CNTFR, IL22, and IL21 genes but did not provide any obvious clues to the molecular mechanism underlying this tumor subtype. Once confirmed on a larger number of patients, the results of the present study could be used for clinical and therapeutic management of patients at the time of diagnosis.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U563 Centre de physiopathologie Toulouse Purpan, Toulouse, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Lamant
authors.forename: Aurélien
authors.initials: A
authors.lastname: de Reyniès
authors.forename: Marie-Michèle
authors.initials: MM
authors.lastname: Duplantier
authors.forename: David S
authors.initials: DS
authors.lastname: Rickman
authors.forename: Frédérique
authors.initials: F
authors.lastname: Sabourdy
authors.forename: Sylvie
authors.initials: S
authors.lastname: Giuriato
authors.forename: Laurence
authors.initials: L
authors.lastname: Brugières
authors.forename: Philippe
authors.initials: P
authors.lastname: Gaulard
authors.forename: Estelle
authors.initials: E
authors.lastname: Espinos
authors.forename: Georges
authors.initials: G
authors.lastname: Delsol
mesh_terms: D000077548:Anaplastic Lymphoma Kinase; D045744:Cell Line, Tumor; D048430:Cell Shape; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D017728:Lymphoma, Large-Cell, Anaplastic / Q000145:classification / Q000201:enzymology / Q000235:genetics* / Q000473:pathology*; D011505:Protein-Tyrosine Kinases / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases; D046888:Tissue Array Analysis
chemical_list: D012333:RNA, Messenger; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; D011505:Protein-Tyrosine Kinases; D020794:Receptor Protein-Tyrosine Kinases