Distinct Gene Expression Profiles Characterize the Histopathological Stages of Disease in Helicobacter-Induced Mucosa-Associated Lymphoid Tissue Lymphoma

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 100; no. 3; pp. 1292 - 1297
• Main Authors: Mueller, Anne, O'Rourke, Jani, Grimm, Jan, Guillemin, Karen, Dixon, Michael F., Lee, Adrian, Falkow, Stanley
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 04.02.2003; National Acad Sciences; The National Academy of Sciences
• Subjects: Algorithms; Animals; ATP-Binding Cassette, Sub-Family B, Member 1 - metabolism; B lymphocytes; Biological Sciences; Calgranulin A - metabolism; Disease; Disease models; Down-Regulation; Drug resistance; Gene expression; Genes; Genetics; Helicobacter - metabolism; Helicobacter pylori - genetics; Helicobacter pylori - metabolism; Immune response; Lesions; Lymphocytes; Lymphoid Tissue - microbiology; Lymphoma; Lymphoma - microbiology; Mice; Mice, Inbred BALB C; Mucosa associated lymphoid tissue lymphoma; Mucous Membrane - microbiology; Nucleic Acid Hybridization; Oligonucleotide Array Sequence Analysis; Pathology; Receptors; RNA, Messenger - metabolism; Stomach; Up-Regulation
• ISSN: 0027-8424; 1091-6490; 1091-6490
• DOI: 10.1073/pnas.242741699

Long-term colonization of humans with Helicobacter pylori can cause the development of gastric B cell mucosa-associated lymphoid tissue lymphoma, yet little is known about the sequence of molecular steps that accompany disease progression. We used microarray analysis and laser microdissection to identify gene expression profiles characteristic and predictive of the various histopathological stages in a mouse model of the disease. The initial step in lymphoma development is marked by infiltration of reactive lymphocytes into the stomach and the launching of a mucosal immune response. Our analysis uncovered molecular markers of both of these processes, including genes coding for the immunoglobulins and the small proline-rich protein Sprr 2A. The subsequent step is characterized histologically by the antigen-driven proliferation and aggregation of B cells and the gradual appearance of lymphoepithelial lesions. In tissues of this stage, we observed increased expression of genes previously associated with malignancy, including the laminin receptor-1 and the multidrug-resistance channel MDR-1. Finally, we found that the transition to destructive lymphoepithelial lesions and malignant lymphoma is marked by an increase in transcription of a single gene encoding calgranulin A/Mrp-8.