title: The prognostic significance of CDKN2A, CDKN2B and MTAP inactivation in B-lineage acute lymphoblastic leukemia of childhood. Results of the EORTC studies 58881 and 58951.
abstract: OBJECTIVE
  Deletion and methylation of the 9p21 chromosomal region are frequent in childhood acute lymphoblastic leukemia (ALL) but the prognostic significance is controversial. They inactivate CDKN2A, a gene encoding both p16INKa and p14ARF and, in some cases, contiguous genes that may influence chemosensitivity, such as CDKN2B encoding p15INKb or MTAP encoding methylthioadenosine phosphorylase.
  
  
  METHODS
  CDKN2A inactivation by deletion or methylation was studied using gene dosage and methyl-specific polymerase chain reaction.
  
  
  RESULTS
  Bi-allelic and mono-allelic inactivation were found in, respectively, 38 (17%) and 31 (14%) of 227 children with B-lineage ALL enrolled in EORTC trials. Although CDKN2A inactivation was more often associated with poor prognostic features in B-lineage ALL, it failed to influence the outcome of the patients significantly. Bi-allelic CDKN2B and MTAP co-inactivation were found in 36 (16%) and 24 (11%) of patients, respectively, and did not influence the 6-year event-free survival rate either, even when the analysis was restricted to CDKN2A inactivated ALL.
  
  
  CONCLUSIONS
  In this study of 227 cases of childhood B-lineage ALL, inactivation of CDKN2A, CDKN2B and MTAP did not influences the patients' outcome.
authors.affiliation: AP-HP, Paris, France.
authors.forename: Delphine
authors.initials: D
authors.lastname: Mirebeau
authors.forename: Cécile
authors.initials: C
authors.lastname: Acquaviva
authors.forename: Stefan
authors.initials: S
authors.lastname: Suciu
authors.forename: Raphaëlle
authors.initials: R
authors.lastname: Bertin
authors.forename: Nicole
authors.initials: N
authors.lastname: Dastugue
authors.forename: Alain
authors.initials: A
authors.lastname: Robert
authors.forename: Patrick
authors.initials: P
authors.lastname: Boutard
authors.forename: Francoise
authors.initials: F
authors.lastname: Méchinaud
authors.forename: Emmanuel
authors.initials: E
authors.lastname: Plouvier
authors.forename: Jacques
authors.initials: J
authors.lastname: Otten
authors.forename: Etienne
authors.initials: E
authors.lastname: Vilmer
authors.forename: Hélène
authors.initials: H
authors.lastname: Cavé
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D050762:Cyclin-Dependent Kinase Inhibitor p15 / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics; D020868:Gene Silencing; D006801:Humans; D007223:Infant; D008869:Microtubule-Associated Proteins / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000401:mortality; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics* / Q000401:mortality; D011379:Prognosis; D015996:Survival Rate; D016896:Treatment Outcome
chemical_list: C493966:CDKN2B protein, human; D050762:Cyclin-Dependent Kinase Inhibitor p15; D019941:Cyclin-Dependent Kinase Inhibitor p16; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins