Cancer/testis genes in multiple myeloma: expression patterns and prognosis value determined by microarray analysis.
Cancer-testis (CT) Ags are expressed in testis and malignant tumors but rarely in nongametogenic tissues. Due to this pattern, they represent attractive targets for cancer vaccination approaches. The aims of the present study are: 1) to assess the expression of CT genes on a pangenomic base in multiple myeloma (MM); 2) to assess the prognosis value of CT gene expression; and 3) to provide selection strategies for CT Ags in clinical vaccination trials. We report the expression pattern of CT genes in purified MM cells (MMC) of 64 patients with newly diagnosed MM and12 patients with monoclonal gammopathy of unknown significance, in normal plasma cell and B cell samples, and in 20 MMC lines. Of the 46 CT genes interrogated by the Affymetrix HG-U133 set arrays, 35 are expressed in the MMC of at least one patient. Of these, 25 are located on chromosome X. The expression of six CT genes is associated with a shorter event-free survival. The MMC of 98% of the patients express at least one CT gene, 86% at least two, and 70% at least three CT genes. By using a set of 10 CT genes including KM-HN-1, MAGE-C1, MAGE-A3/6/12, MAGE-A5, MORC, DDX43, SPACA3, SSX-4, GAGE-1-8, and MAGE-C2, a combination of at least three CT genes-desirable for circumventing tumor escape mechanisms-is obtained in the MMC of 67% of the patients. Provided that the immunogenicity of the products of these 10 CT genes is confirmed, gene expression profiling could be useful in identifying which CT Ags could be used to vaccinate a given patient.
Condomines
Maud
M
Institute of Research in Biotherapy, Centre Hospitalier Universitaire Montpellier, Montpellier, France.
Hose
Dirk
D
Raynaud
Pierre
P
Hundemer
Michael
M
De Vos
John
J
Baudard
Marion
M
Moehler
Thomas
T
Pantesco
Véronique
V
Moos
Marion
M
Schved
Jean-François
JF
Rossi
Jean-François
JF
Rème
Thierry
T
Goldschmidt
Hartmut
H
Klein
Bernard
B
D000951:Antigens, Neoplasm / Q000096:biosynthesis* / Q000235:genetics; D019496:Cancer Vaccines / Q000235:genetics / Q000627:therapeutic use; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D020411:Oligonucleotide Array Sequence Analysis; D011237:Predictive Value of Tests; D011379:Prognosis
D000951:Antigens, Neoplasm; D019496:Cancer Vaccines