title: High-density screening reveals a different spectrum of genomic aberrations in chronic lymphocytic leukemia patients with 'stereotyped' IGHV3-21 and IGHV4-34 B-cell receptors.
abstract: BACKGROUND
  The existence of multiple subsets of chronic lymphocytic leukemia expressing 'stereotyped' B-cell receptors implies the involvement of antigen(s) in leukemogenesis. Studies also indicate that 'stereotypy' may influence the clinical course of patients with chronic lymphocytic leukemia, for example, in subsets with stereotyped IGHV3-21 and IGHV4-34 B-cell receptors; however, little is known regarding the genomic profile of patients in these subsets.
  
  
  METHODS
  We applied 250K single nucleotide polymorphism-arrays to study copy-number aberrations and copy-number neutral loss-of-heterozygosity in patients with stereotyped IGHV3-21 (subset #2, n=29), stereotyped IGHV4-34 (subset #4, n=17; subset #16, n=8) and non-subset #2 IGHV3-21 (n=13) and non-subset #4/16 IGHV4-34 (n=34) patients.
  
  
  RESULTS
  Over 90% of patients in subset #2 and non-subset #2 carried copy-number aberrations, whereas 75-76% of patients in subset #4 and subset #16 showed copy-number aberrations. Subset #2 and non-subset #2 patients also displayed a higher average number of aberrations compared to patients in subset #4. Deletion of 13q was the only known recurrent aberration detected in subset #4 (35%); this aberration was even more frequent in subset #2 (79%). del(11q) was more frequent in subset #2 and non-subset #2 (31% and 23%) patients than in subset #4 and non-subset #4/16 patients. Recurrent copy-number neutral loss-of-heterozygosity was mainly detected on chromosome 13q, independently of B-cell receptor stereotypy.
  
  
  CONCLUSIONS
  Genomic aberrations were more common in subset #2 and non-subset #2 than in subset #4. The particularly high frequency of del(11q) in subset #2 may be linked to the adverse outcome reported for patients in this subset. Conversely, the lower prevalence of copy-number aberrations and the absence of poor-prognostic aberrations in subset #4 may reflect an inherently low-proliferative disease, which would prevent accumulation of genomic alterations.
authors.affiliation: Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala University, SE-751-85 Uppsala, Sweden.
authors.forename: Millaray
authors.initials: M
authors.lastname: Marincevic
authors.forename: Nicola
authors.initials: N
authors.lastname: Cahill
authors.forename: Rebeqa
authors.initials: R
authors.lastname: Gunnarsson
authors.forename: Anders
authors.initials: A
authors.lastname: Isaksson
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Mansouri
authors.forename: Hanna
authors.initials: H
authors.lastname: Göransson
authors.forename: Markus
authors.initials: M
authors.lastname: Rasmussen
authors.forename: Mattias
authors.initials: M
authors.lastname: Jansson
authors.forename: Fergus
authors.initials: F
authors.lastname: Ryan
authors.forename: Karin
authors.initials: K
authors.lastname: Karlsson
authors.forename: Hans-Olov
authors.initials: HO
authors.lastname: Adami
authors.forename: Fred
authors.initials: F
authors.lastname: Davi
authors.forename: Jesper
authors.initials: J
authors.lastname: Jurlander
authors.forename: Gunnar
authors.initials: G
authors.lastname: Juliusson
authors.forename: Kostas
authors.initials: K
authors.lastname: Stamatopoulos
authors.forename: Richard
authors.initials: R
authors.lastname: Rosenquist
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D002869:Chromosome Aberrations; D005260:Female; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics; D007135:Immunoglobulin Variable Region / Q000235:genetics; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics* / Q000276:immunology; D008297:Male; D008403:Mass Screening; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D011947:Receptors, Antigen, B-Cell
chemical_list: D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D011947:Receptors, Antigen, B-Cell