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Blood, Vol. 95 No. 4 (February 15), 2000:
pp. 1180-1187
Genetic aberrations common in gastric high-grade large B-cell
lymphoma
Petr Starostik,
Axel Greiner,
Anja Schultz,
Andreas Zettl,
Katharina Peters,
Andreas Rosenwald,
Mariele Kolve, and
Hans Konrad Müller-Hermelink
From the Institute of Pathology and Division of Medicine, Wuerzburg
University, Wuerzburg, Germany.
Genetic aberrations associated with the development of extranodal
high-grade large B-cell lymphoma originating in the stomach have not
been fully identified yet. We analyzed 31 such lymphomas using 73 microsatellite markers for allelic imbalance and microsatellite instability. The highest frequency (42%) of loss of heterozygosity (LOH) was found on the long arm of chromosome 6. We identified 2 LOH
hot spots on 6q21-22.1 and 6q23.3-25, flanked by markers D6S246-D6S261
and D6S310-D6S441, respectively, containing putative tumor suppressor
genes (TSGs). These 6q aberrations were found to be the sole allelic
imbalance in 1 patient only; they were mostly accompanied by additional
abnormalities. Several known TSGs, namely, the APC, p15/p16, p53, and
DCC genes, were found to suffer frequent LOH during lymphomagenesis.
LOH was also detected in regions containing putative TSGs on 7q and
13q14. Frequent amplification of genomic material was found in the 2p,
3q27 at the BCL-6 gene locus, 6p, 7q, 11q23-24 at the MLL gene locus, and 18q regions. Analysis of the pattern of occurrence of these aberrations revealed an association of the amplification of the MLL
gene region with LOH at the p53 locus (P = .02). Only low frequency of microsatellite instability (MSI) was detected in these
lymphomas and MSI incidence increased with age (P = .01). Karyotypic instability thus plays the main role in the development of
gastric high-grade large B-cell lymphoma. Common genetic aberrations responsible for lymphomagenesis are deletions of 6q, loss of p53, and
amplification of the 3q27 and the MLL gene regions.
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