Gain of 7q22 Is the Most Common Genomic Alteration Identified in an Oligonucleotide-Based Array CGH Analysis of Diffuse Large B-Cell Lymphomas
EA Medina, AR Bolla, RL Bandi, RS Robetorye. The University of Texas Health Science Center at San Antonio, San Antonio, TX
Background: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma in the Western world. While 40-50% of patients with this lymphoma respond well to therapy with prolonged survival, for the majority, this malignancy is rapidly fatal. This varied clinical response is likely due to underlying molecular heterogeneity in DLBCL. Gene expression analyses have revealed clinically relevant subtypes and suggested signaling pathways for therapeutic targeting. Despite these advances, there is a need to identify genes that have a critical function in DLBCL in order to broaden the number of potential therapeutic targets for this highly heterogeneous malignancy.
Design: Sixty nodal and extranodal DLBCLs and 28 DLBCL cell lines were analyzed using Agilent Human Genome 44K or 105K CGH oligonucleotide arrays (Agilent Technologies, Santa Clara, CA). Slides were scanned with an Agilent Scanner, and the data were analyzed with Agilent Feature Extraction, Agilent CGH Analytics, and Nexus Copy Number (Biodiscovery, Inc., El Segundo, CA) software.
Results: 60% of cases exhibited a gain in chromosomal material on chromosome 7q22; this was the most common genomic abnormality observed in these 88 cases of DLBCL (Figure 1).
Patients whose malignancies exhibited this particular abnormality showed an increased survival of approximately 30% compared with those that did not. The smallest common region of gain in these cases consisted of a 150 kb stretch of DNA that contains a gene that encodes the zinc finger transcription factor protein ZKSCAN1. ZKSCAN1 protein expression was increased in cases that exhibited gains of 7q22.
Conclusions: ZKSCAN1 has previously been implicated in the regulation of cell proliferation. It also appears to be regulated by the serine/threonine kinase ataxia-telangiectasia mutated (ATM) gene product. ATM is activated in response to genotoxic insults and regulates proteins involved in the DNA damage checkpoint, cell cycle arrest, DNA repair, and apoptosis. Therefore, ZKSCAN1 may regulate the proliferation and survival of lymphoma cells in DLBCLs that exhibit a gain of 7q22.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 186, Monday Morning