Frequent occurrence of deletions in primary mediastinal B-cell lymphoma.
Primary mediastinal B-cell lymphoma (PMBCL) is a distinct subtype of diffuse large B-cell lymphoma. PMBCL has been previously studied with a variety of genomic techniques resulting in frequent detection of chromosomal gains; however, chromosomal losses have been rarely reported. This finding contrasts many other types of lymphoma, in which deletions are common. We hypothesize that segmental losses do exist but may have escaped detection by methods used in the previous studies. Using array comparative genomic hybridization to a tiling-resolution microarray encompassing the entire human genome, PMBCL samples were analyzed for genomic copy number alterations. An almost equal number of gains and losses of chromosomal material were detected throughout the genome (216 vs. 193, respectively). A selection of these DNA copy number alterations were confirmed by quantitative real-time PCR. Recurrent gains were detected at all previously reported regions of gain, including 9p seen in approximately 70% of cases. Recurrent chromosomal losses were observed at 1p, 3p, 4q, 6q, 7p, and 17p, with a novel event at 1p13.1-p13.2 representing the most frequent at 42% of cases analyzed. We conclude that consistent losses are present in the PMBCL genome. Given the similar frequency of losses to that of segmental gains of DNA, they are likely to play an important role in the pathogenesis of PMBCL.
Kimm
Lindsey R
LR
Department of Cancer Genetics and Developmental Biology, British Columbia Cancer Research Centre, Vancouver, BC, Canada.
deLeeuw
Ronald J
RJ
Savage
Kerry J
KJ
Rosenwald
Andreas
A
Campo
Elias
E
Delabie
Jan
J
Ott
German
G
Muller-Hermelink
Hans-Konrad
HK
Jaffe
Elaine S
ES
Rimsza
Lisa M
LM
Weisenburger
Dennis D
DD
Chan
Wing C
WC
Staudt
Louis M
LM
Connors
Joseph M
JM
Gascoyne
Randy D
RD
Lam
Wan L
WL
D000328:Adult; D000368:Aged; D002872:Chromosome Deletion; D002877:Chromosomes, Human; D005260:Female; D015894:Genome, Human; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse / Q000145:classification / Q000235:genetics*; D008297:Male; D008479:Mediastinal Neoplasms / Q000235:genetics*; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis