Biological Characterization of Stage I Follicular Lymphoma According to Extranodal or Nodal Primary Origin and t(14;18) Status Using High-Resolution Array-Based Comparative Genomic Hybridization (aCGH)
OK Weinberg, L Ma, K Seo, R Hoppe, DA Arber. Stanford University, Stanford, CA
Background: We have recently shown that in patients with low stage follicular lymphoma (FL), the status of t(14;18) appears to be more predictive of clinical outcome than origin from an extranodal versus nodal site. Little is know of the molecular genetics of t(14;18)-negative FL, or of the genetic differences between nodal and extranodal FL. The goal of the current study was to characterize stage I FL using aCGH.
Design: Twenty stage I FL cases, 10 each with and without evidence of t(14;18), diagnosed at Stanford University were studied, including 9 primary extranodal (thyroid, ocular, submandibular gland, parotid, stomach, duodenum) and 11 nodal cases. Five extranodal FL cases were t(14;18)+ and 4 were negative for the translocation. DNA was isolated from paraffin blocks and all 20 cases were hybridized to the Agilent Human Genome CGH 4 x 44 K Microarray (Agilent Technologies, Santa Clara, CA). The obtained data was analyzed using both Agilent DNA Analytics 4.0 Software and CGH-miner (Stanford, CA) software, and only gains and losses identified by both methods were considered significant. Cases were compared both by origin from extranodal versus nodal site and by t(14;18) status.
Results: The t(14;18)-negative FL contained gains on chromosome 1q42, 3q13, 3p22, 14q12 and deletion of 6q12 (regulating synaptic membrane, RIMS1) as compared to t(14;18)+ cases. The region with the most gains was 14q12, and this gain has not been reported in prior CGH studies of FL. Genes in chromosomal regions with established importance gained in t(14;18)-negative cases include germinal center expressed transcript 2 (GCET2), interferon regulatory factor 9 (ISGF3G), ring finger protein (RNF31), and B and T lymphocyte attenuator (BTLA). The extranodal FL cases differed from nodal by gain on chromosome 3p22, 4q34, 7p15 and 17p13. Genes in these regions with established importance gained in extranodal FL include transforming growth factor beta receptor (TGFBR2), interferon regulatory factor 2 (IRF2), methyl-CpG binding domain protein (MBD4) and TP53.
Conclusions: In stage I FL, cases lacking t(14;18) contained significant gains in chromosome 1q, 3q, 3p, 14q and a loss in 6q as compared to t(14;18)+ cases. Extranodal FL cases were characterized by significant gains in 3p, 4q, 7p and 17p as compared to nodal FL. These findings provide clues for possible biological differences associated with t(14;18) status and origin from extranodal versus nodal site in low-stage FL.
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 144, Tuesday Morning