Identified hidden genomic changes in mantle cell lymphoma using high-resolution single nucleotide polymorphism genomic array.
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.
Kawamata
Norihiko
N
Hematology/Oncology, Cedars-Sinai Medical Center/UCLA School of Medicine, Los Angeles, Calif., USA.
Ogawa
Seishi
S
Gueller
Saskia
S
Ross
Samuel H
SH
Huynh
Thien
T
Chen
John
J
Chang
Andrew
A
Nabavi-Nouis
Shayan
S
Megrabian
Nairi
N
Siebert
Reiner
R
Martinez-Climent
Jose A
JA
Koeffler
H Phillip
HP
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