title: Cancer testis antigens in newly diagnosed and relapse multiple myeloma: prognostic markers and potential targets for immunotherapy.
abstract: BACKGROUND
  In multiple myeloma, expression of cancer testis antigens may provide prognostic markers and potential targets for immunotherapy. Expression at relapse has not yet been evaluated for a large panel of cancer testis antigens which can be classified by varying expression in normal tissue: restricted to testis, expressed in testis and brain and not restricted but selectively expressed in testis.
  
  
  METHODS
  Evaluation of cancer testis antigen expression was made in newly diagnosed multiple myeloma cases (HOVON-65/GMMG-HD4 trial; n = 320) and in relapse cases (APEX, SUMMIT, CREST trials; n = 264). Presence of expression using Affymetrix GeneChips was determined for 123 cancer testis antigens. Of these 87 had a frequency of more than 5% in the newly diagnosed and relapsed patients, and were evaluated in detail.
  
  
  RESULTS
  Tissue restriction was known for 58 out of 87 cancer testis antigens. A significantly lower frequency of presence calls in the relapsed compared to newly diagnosed cases was found for 3 out of 13 testis restricted genes, 2 out of 7 testis/brain restricted genes, and 17 out of 38 testis selective genes. MAGEC1, MAGEB2 and SSX1 were the most frequent testis-restricted cancer testis antigens in both data sets. Multivariate analysis demonstrated that presence of MAGEA6 and CDCA1 were clearly associated with shorter progression free survival, and presence of MAGEA9 with shorter overall survival in the set of newly diagnosed cases. In the set of relapse cases, presence of CTAG2 was associated with shorter progression free survival and presence of SSX1 with shorter overall survival.
  
  
  CONCLUSIONS
  Relapsed multiple myeloma reveals extensive cancer testis antigen expression. Cancer testis antigens are confirmed as useful prognostic markers in newly diagnosed multiple myeloma patients and in relapsed multiple myeloma patients. The HOVON-65/GMMG-HD4 trial is registered under Dutch trial register n. NTR-213. CREST, SUMMIT and APEX trials were registered under ns. M34100-024, M34100-025 and NCT00049478/NCT00048230, respectively.
authors.affiliation: Department of Hematology, Erasmus Medical Center Rotterdam, Rotterdam, The Netherlands. m.vanduin@erasmusmc.nl
authors.forename: Mark
authors.initials: M
authors.lastname: van Duin
authors.forename: Annemiek
authors.initials: A
authors.lastname: Broyl
authors.forename: Yvonne
authors.initials: Y
authors.lastname: de Knegt
authors.forename: Hartmut
authors.initials: H
authors.lastname: Goldschmidt
authors.forename: Paul G
authors.initials: PG
authors.lastname: Richardson
authors.forename: Wim C J
authors.initials: WC
authors.lastname: Hop
authors.forename: Bronno
authors.initials: B
authors.lastname: van der Holt
authors.forename: Debora
authors.initials: D
authors.lastname: Joseph-Pietras
authors.forename: George
authors.initials: G
authors.lastname: Mulligan
authors.forename: Rachel
authors.initials: R
authors.lastname: Neuwirth
authors.forename: Surinder S
authors.initials: SS
authors.lastname: Sahota
authors.forename: Pieter
authors.initials: P
authors.lastname: Sonneveld
mesh_terms: D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D014408:Biomarkers, Tumor / Q000096:biosynthesis*; D018572:Disease-Free Survival; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007167:Immunotherapy; D008297:Male; D009101:Multiple Myeloma / Q000378:metabolism* / Q000401:mortality* / Q000517:prevention & control; D012008:Recurrence; D015996:Survival Rate; D013736:Testicular Neoplasms
chemical_list: D000951:Antigens, Neoplasm; D014408:Biomarkers, Tumor