title: The prognostic significance of various 13q14 deletions in chronic lymphocytic leukemia.
abstract: OBJECTIVE
  To further our understanding of the biology and prognostic significance of various chromosomal 13q14 deletions in chronic lymphocytic leukemia (CLL).
  
  
  METHODS
  We analyzed data from SNP 6.0 arrays to define the anatomy of various 13q14 deletions in a cohort of 255 CLL patients and have correlated two subsets of 13q14 deletions (type I exclusive of RB1 and type II inclusive of RB1) with patient survival. Furthermore, we measured the expression of the 13q14-resident microRNAs by quantitative PCR (Q-PCR) in 242 CLL patients and subsequently assessed their prognostic significance. We sequenced all coding exons of RB1 in patients with monoallelic RB1 deletion and have sequenced the 13q14-resident miR locus in all patients.
  
  
  RESULTS
  Large 13q14 (type II) deletions were detected in approximately 20% of all CLL patients and were associated with shortened survival. A strong association between 13q14 type II deletions and elevated genomic complexity, as measured through CLL-FISH or SNP 6.0 array profiling, was identified, suggesting that these lesions may contribute to CLL disease evolution through genomic destabilization. Sequence and copy number analysis of the RB1 gene identified a small CLL subset that is RB1 null. Finally, neither the expression levels of the 13q14-resident microRNAs nor the degree of 13q14 deletion, as measured through SNP 6.0 array-based copy number analysis, had significant prognostic importance.
  
  
  CONCLUSIONS
  Our data suggest that the clinical course of CLL is accelerated in patients with large (type II) 13q14 deletions that span the RB1 gene, therefore justifying routine identification of 13q14 subtypes in CLL management.
authors: Division of Hematology and Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan 48109, USA.
authors: Peter
authors: P
authors: Ouillette
authors: Roxane
authors: R
authors: Collins
authors: Sajid
authors: S
authors: Shakhan
authors: Jinghui
authors: J
authors: Li
authors: Cheng
authors: C
authors: Li
authors: Kerby
authors: K
authors: Shedden
authors: Sami N
authors: SN
authors: Malek
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002503:Centromere / Q000235:genetics; D056905:Chromosome Breakpoints; D002872:Chromosome Deletion; D002883:Chromosomes, Human, Pair 14; D015331:Cohort Studies; D005260:Female; D016368:Frameshift Mutation; D018628:Gene Dosage; D006801:Humans; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000473:pathology; D008297:Male; D035683:MicroRNAs / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D008969:Molecular Sequence Data; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D016160:Retinoblastoma Protein / Q000096:biosynthesis / Q000235:genetics; D015996:Survival Rate; D016615:Telomere / Q000235:genetics
chemical_list: C505361:MIRN15 microRNA, human; C505362:MIRN16 microRNA, human; D035683:MicroRNAs; D012333:RNA, Messenger; D016160:Retinoblastoma Protein