title: Differential genetic and functional markers of second neoplasias in Hodgkin's disease patients.
abstract: OBJECTIVE
  The mechanisms involved in the appearance of a second neoplasia in patients with Hodgkin's disease (HD) are probably related to the genomic damage induced by the treatments administered and its repair. Here, we searched for some constitutive molecular mechanisms that in a basal manner may influence the behavior of HD patients.
  
  
  METHODS
  We aimed to evaluate with the Comet Assay whether baseline, induced, and unrepaired DNA damage differ between HD patients who did not develop a second neoplasia (HD-NST), HD patients who developed a second tumor (HD-ST), and healthy individuals; and to identify, through cDNA microarray hybridization, an expression signature of genes that could discriminate between the three groups.
  
  
  RESULTS
  Baseline, induced, and unrepaired DNA damage was higher in HD-ST than in HD-NST and higher in the second group than in healthy donors. The genomic approach revealed two sets of genes that discriminated between healthy subjects and patients and between the three sets of individuals. Hsp40, RAD50, TPMT, Rap2a, E2F2, EPHX2, TBX21, and BATF were validated by reverse transcription-PCR.
  
  
  CONCLUSIONS
  Functional and genomic techniques revealed that alterations in cell cycle, repair, detoxification, and stress response pathways could be involved in the development of HD and in the occurrence of a primary second neoplasia in these patients. Both approaches may be useful as biological markers in the clinical setting.
authors.affiliation: Departments of Medical Oncology and Radiation Oncology, Hospital Universitario Puerta de Hierro, Majadahonda; and Molecular Diagnostic Unit, Molecular Pathology Program, Spanish Cancer Research Center, Madrid, Spain.
authors.forename: Yolanda
authors.initials: Y
authors.lastname: Lorenzo
authors.forename: Mariano
authors.initials: M
authors.lastname: Provencio
authors.forename: Luís
authors.initials: L
authors.lastname: Lombardía
authors.forename: Raquel
authors.initials: R
authors.lastname: Díaz
authors.forename: Javier
authors.initials: J
authors.lastname: Silva
authors.forename: Mercedes
authors.initials: M
authors.lastname: Herrera
authors.forename: Jose M
authors.initials: JM
authors.lastname: García
authors.forename: Cristina
authors.initials: C
authors.lastname: Peña
authors.forename: Vanesa
authors.initials: V
authors.lastname: García
authors.forename: Jesús
authors.initials: J
authors.lastname: Romero
authors.forename: Gemma
authors.initials: G
authors.lastname: Domínguez
authors.forename: Félix
authors.initials: F
authors.lastname: Bonilla
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002648:Child; D004249:DNA Damage / Q000235:genetics / Q000502:physiology; D004260:DNA Repair / Q000235:genetics / Q000502:physiology; D005260:Female; D006689:Hodgkin Disease / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016609:Neoplasms, Second Primary / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D055815:Young Adult
chemical_list: D014408:Biomarkers, Tumor