Distinct gene expression profiles: nodal versus extranodal diffuse large B-cell lymphoma.
BACKGROUND
Approximately one third of diffuse large B-cell lymphomas (DLBCL) arises from tissues different from the lymph node. Perceived differences in outcome between extranodal and nodal DLBCL raise the possibility that these subgroups may represent different biological and clinical entities.


METHODS
Microarray GeneChip technology was used for global gene expression profiles from nodal (n = 19) and extranodal (n = 8) DLBCL, to examine possible differences between these subgroups. Quantitative RT-PCR was employed for validation of microarray data. Differential expression levels of p16 (CDKN2A) were confirmed by means of immunohistochemistry on a tissue microarray comprising more than 200 lymphoma samples.


RESULTS
A total of 218, over (124)- and underexpressed (94) genes were found to be differentially expressed in extranodal DLBCL compared with nodal DLBCL, including cytokines/chemokines, chromosome-replication-related genes and DNA repair genes. Quantitative RT-PCR confirmed the microarray data. A higher rate of p16 positivity was found in extranodal lymphomas. However, prognostic importance of p16 was associated with nodal rather than extranodal lymphomas.


CONCLUSIONS
Our data suggest that a better distinction of these subgroups based on molecular classifiers is feasible and may greatly facilitate the determination of specific relevant clinical features and therapeutic implications of DLBCL with primary extranodal or nodal location.
Jehan
Zeenath
Z
Human Cancer Genomic Research, King Fahad National Centre for Children's Cancer and Research,Riyadh, Saudi Arabia.
Siraj
Abdul K
AK
Abubaker
Jehad
J
Ruiz
Christian
C
Simon
Ronald
R
Sultana
Mehar
M
Uddin
Shahab
S
Bavi
Prashant
P
Hussain
Azhar
A
Razack
Shirin
S
Ezzat
Adnan
A
Al-Dayel
Fouad
F
Sauter
Guido
G
Al-Kuraya
Khawla S
KS
D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D019942:Genes, p16 / Q000502:physiology; D006801:Humans; D008198:Lymph Nodes / Q000378:metabolism; D016393:Lymphoma, B-Cell / Q000235:genetics*; D012313:RNA / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012313:RNA