title: Acquired chromosomal anomalies in chronic lymphocytic leukemia patients compared with more than 50,000 quasi-normal participants.
abstract: Pretherapy patients with chronic lymphocytic leukemia (CLL) from US Intergroup trial E2997 were analyzed with single nucleotide polymorphism microarrays to detect acquired chromosomal anomalies. The four CLL-typical anomalies (11q-, +12, 13q-, and 17p-) were found at expected frequencies. Acquired anomalies in other regions account for 70% of the total detected anomalies, and their number per participant has a significant effect on progression-free survival after adjusting for the effects of 17p- (and other covariates). These results were compared with those from a previous study of more than 50,000 participants from the GENEVA consortium of genome-wide association studies, which analyzed individuals with a variety of medical conditions and healthy controls. The percentage of individuals with acquired anomalies is vastly different between the two studies (GENEVA 0.8%; E2997 80%). The composition of the anomalies also differs, with GENEVA having a higher percentage of acquired uniparental disomies and a lower percentage of deletions. The four common CLL anomalies are among the most frequent in GENEVA participants, some of whom may have CLL-precursor conditions or early stages of CLL. However, the patients from E2997 (and other studies of symptomatic CLL) have recurrent acquired anomalies that were not found in GENEVA participants, thus identifying genomic changes that may be unique to symptomatic stages of CLL.
authors.affiliation: Biostatistics Department, University of Washington, Seattle, WA, USA. Electronic address: cclaurie@u.washington.edu.
authors.forename: Cathy C
authors.initials: CC
authors.lastname: Laurie
authors.affiliation: Biostatistics Department, University of Washington, Seattle, WA, USA.
authors.forename: Cecelia A
authors.initials: CA
authors.lastname: Laurie
authors.affiliation: Department of Laboratory Medicine and Pathology, Cytogenetics Laboratory, Mayo Clinic, Rochester, MN, USA.
authors.forename: Stephanie A
authors.initials: SA
authors.lastname: Smoley
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Carlson
authors.affiliation: Sarah Cannon Research Institute, Nashville, TN, USA.
authors.forename: Ian
authors.initials: I
authors.lastname: Flinn
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA; University of Kansas Medical Center, Kansas City, KS, USA.
authors.forename: Brooke L
authors.initials: BL
authors.lastname: Fridley
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, WA, USA; PhenoPath Laboratories, Seattle, WA, USA.
authors.forename: Harvey A
authors.initials: HA
authors.lastname: Greisman
authors.affiliation: Barts Cancer Institute, Queen Mary, University of London, London, UK.
authors.forename: John G
authors.initials: JG
authors.lastname: Gribben
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA; Department of Immunology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Diane F
authors.initials: DF
authors.lastname: Jelinek
authors.affiliation: Biostatistics Department, University of Washington, Seattle, WA, USA.
authors.forename: Sarah C
authors.initials: SC
authors.lastname: Nelson
authors.affiliation: The North Division of Montefiore Medical Center, Bronx, NY, USA.
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Paietta
authors.affiliation: Department of Health Sciences Research, Mayo Clinic, Rochester, MN, USA.
authors.forename: Dan
authors.initials: D
authors.lastname: Schaid
authors.affiliation: Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute, Boston, MA, USA.
authors.forename: Zhuoxin
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
authors.forename: Martin S
authors.initials: MS
authors.lastname: Tallman
authors.affiliation: Division of Clinical Pharmacology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Richard
authors.initials: R
authors.lastname: Weinshilboum
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Neil E
authors.initials: NE
authors.lastname: Kay
authors.affiliation: Division of Hematology, Mayo Clinic, Rochester, MN, USA.
authors.forename: Tait D
authors.initials: TD
authors.lastname: Shanafelt
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002869:Chromosome Aberrations; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000235:genetics; D002874:Chromosome Mapping; D017326:Clinical Trials, Phase III as Topic; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009030:Mosaicism; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D016016:Proportional Hazards Models; D012306:Risk; D024182:Uniparental Disomy
keywords: Chromosomal aberration; cancer precursor condition; chromosomal mosaic; chronic lymphocytic leukemia; cytogenetics