Detection of the bcl-2 t(14;18) translocation and proto-oncogene expression in primary intraocular lymphoma.
OBJECTIVE
Primary intraocular lymphoma (PIOL) is a diffuse large B cell lymphoma that initially infiltrates the retina, vitreous, or optic nerve head, with or without central nervous system involvement. This study examined the expression of the bcl-2 t(14;18) translocation, the bcl-10 gene, and high expression of bcl-6 mRNA in PIOL cells.


METHODS
Microdissection and PCR analysis were used to examine vitreous specimens in patients with PIOL for the presence of bcl-2 t(14;18) translocations, the bcl-10 gene, and expression of bcl-6 mRNA. A medical record review was also conducted to determine whether the bcl-2 t(14;18) translocation correlated with prognosis.


RESULTS
Forty of 72 (55%) PIOL patients expressed the bcl-2 t(14;18) translocation at the major breakpoint region. Fifteen of 68 (22%) patients expressed the translocation at the minor cluster region. The bcl-10 gene was detected in 6 of 26 (23%) patients, whereas 4 of 4 (100%) PIOL patients expressed higher levels of bcl-6 mRNA compared with inflammatory lymphocytes. An analysis of clinical outcome in 23 PIOL patients revealed no significant association between bcl-2 t(14;18) translocations and survival or relapse. However, patients with the translocation were significantly younger.


CONCLUSIONS
PIOL has unique molecular patterns of bcl-2, bcl-10, and bcl-6 when compared with other systemic lymphomas. This study lays the foundation for future studies aimed at exploring the genotypic classification of PIOL based on the quantitative molecular framework of gene expression profiling, with the goal of providing useful adjuncts to the pathologic diagnosis of this complex disease.
Wallace
Dana J
DJ
Laboratory of Immunology, Division of Epidemiology and Clinical Research, National Eye Institute, National Institutes of Health, Bethesda, MD 20895-1857, USA, and Department of Ophthalmology, Tokyo Medical and Dental University, Japan.
Shen
DeFen
D
Reed
George F
GF
Miyanaga
Masaru
M
Mochizuki
Manabu
M
Sen
H Nida
HN
Dahr
Samuel S
SS
Buggage
Ronald R
RR
Nussenblatt
Robert B
RB
Chan
Chi-Chao
CC
D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000074018:B-Cell CLL-Lymphoma 10 Protein; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002887:Chromosomes, Human, Pair 18 / Q000235:genetics*; D004273:DNA, Neoplasm / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D005134:Eye Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D019254:Genes, bcl-2 / Q000235:genetics*; D006801:Humans; D016393:Lymphoma, B-Cell / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger / Q000378:metabolism; D014178:Translocation, Genetic; D014821:Vitrectomy; D014822:Vitreous Body / Q000473:pathology
D048868:Adaptor Proteins, Signal Transducing; D000074018:B-Cell CLL-Lymphoma 10 Protein; C118591:BCL10 protein, human; C084103:BCL6 protein, human; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D012333:RNA, Messenger