Gcet1 (centerin), a highly restricted marker for a subset of germinal center-derived lymphomas.
GCET1 (germinal center B cell-expressed transcript-1) gene codes for a serpin expressed in germinal center (GC) B cells. Following the observation that follicular lymphoma cases exhibit an increased level of Gcet1 expression, compared with follicular hyperplasia, we have characterized Gcet1 protein expression in human tissues, cell lines, and a large series of lymphomas. To this end, we have performed immunohistochemical and Western blot analyses using a newly generated monoclonal antibody that is reactive in paraffin-embedded tissues. Our results demonstrate that Gcet1 is expressed exclusively by neoplasms hypothetically to be arrested at the GC stage of differentiation, including follicular lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, and a subset of diffuse large B-cell lymphoma, T-cell/histiocyte rich B-cell lymphoma, and Burkitt lymphoma. Within these tumors, Gcet-1 protein expression is restricted to a subset of GC B cells, establishing the existence of a distinct heterogeneity among normal and neoplastic GC B cells. None of the other B-cell lymphomas, that is, chronic lymphocytic leukemia, splenic marginal zone lymphoma, and mantle cell lymphoma, was Gcet1(+), which underlines the potential utility of Gcet1 expression in lymphoma diagnosis. The results of RNA and protein expression should prompt further investigation into the role of Gcet1 in regulating B-cell survival.
Montes-Moreno
Santiago
S
Lymphoma Group, Spanish National Cancer Centre (CNIO), Madrid, Spain. smontes@cnio.es
Roncador
Giovanna
G
Maestre
Lorena
L
Martínez
Nerea
N
Sanchez-Verde
Lydia
L
Camacho
Francisca I
FI
Cannata
Jimena
J
Martinez-Torrecuadrada
Jorge L
JL
Shen
Yulei
Y
Chan
Wing C
WC
Piris
Miguel A
MA
D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism*; D015153:Blotting, Western; D002051:Burkitt Lymphoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D018858:Germinal Center / Q000473:pathology*; D006689:Hodgkin Disease / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D006801:Humans; D007124:Immunoenzyme Techniques; D008223:Lymphoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D008224:Lymphoma, Follicular / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D015843:Serpins / Q000235:genetics* / Q000378:metabolism*
D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; C476825:SERPINA9 protein, human; D015843:Serpins