title: Identified hidden genomic changes in mantle cell lymphoma using high-resolution single nucleotide polymorphism genomic array.
abstract: OBJECTIVE
  Mantle cell lymphoma (MCL) is a lymphoma characterized by aberrant activation of CCND1/cyclin D1 followed by sequential genetic abnormalities. Genomic abnormalities in MCL have been extensively examined by classical cytogenetics and microarray-based comparative genomic hybridization techniques, pointing out a number of alterations in genomic regions that correlate with the neoplastic phenotype and survival. Recently, single nucleotide polymorphism genomic microarrays (SNP-chip) have been developed and used for analysis of cancer genomics. This technique allows detection of genomic changes with higher resolution, including loss of heterozygosity without changes of gene dosage, so-called acquired uniparental disomy (aUPD).
  
  
  METHODS
  We have examined 33 samples of MCL (28 primary MCL and 5 cell lines) using the 250,000 SNP-chip from Affymetrix.
  
  
  RESULTS
  Known alterations were confirmed by SNP arrays, including deletion of INK4A/ARF, duplication/amplification of MYC, deletion of ATM, and deletion of TP53. We also identified a duplication/amplification that occurred at 13q involving oncogenic microRNA, miR17-92. We found other genomic abnormalities, including duplication/amplification of cyclin D1, del(1p), del(6q), dup(3q) and dup(18q). Our SNP-chip analysis detected these abnormalities at high resolution, allowing us to narrow the size of the commonly deleted regions, including 1p and 6q. Our SNP-chip analysis detected a number of aUPD sites, including whole chromosome 9 aUPD and 9p aUPD. We also found an MCL case with 19p, leading to homozygous deletion of TNFSF genes.
  
  
  CONCLUSIONS
  SNP-chip analysis detected in MCL very small genomic gains/losses, as well as aUPDs, which could not be detected by more conventional methods.
authors.affiliation: Hematology/Oncology, Cedars-Sinai Medical Center/UCLA School of Medicine, Los Angeles, Calif., USA.
authors.forename: Norihiko
authors.initials: N
authors.lastname: Kawamata
authors.forename: Seishi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Saskia
authors.initials: S
authors.lastname: Gueller
authors.forename: Samuel H
authors.initials: SH
authors.lastname: Ross
authors.forename: Thien
authors.initials: T
authors.lastname: Huynh
authors.forename: John
authors.initials: J
authors.lastname: Chen
authors.forename: Andrew
authors.initials: A
authors.lastname: Chang
authors.forename: Shayan
authors.initials: S
authors.lastname: Nabavi-Nouis
authors.forename: Nairi
authors.initials: N
authors.lastname: Megrabian
authors.forename: Reiner
authors.initials: R
authors.lastname: Siebert
authors.forename: Jose A
authors.initials: JA
authors.lastname: Martinez-Climent
authors.forename: H Phillip
authors.initials: HP
authors.lastname: Koeffler
mesh_terms: D002478:Cells, Cultured; D004252:DNA Mutational Analysis / Q000379:methods* / Q000592:standards; D017353:Gene Deletion; D020440:Gene Duplication; D006801:Humans; D019656:Loss of Heterozygosity; D020522:Lymphoma, Mantle-Cell / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D017384:Sequence Deletion; D024182:Uniparental Disomy