title: Genetic polymorphisms of the XPG and XPD nucleotide excision repair genes in sarcoma patients.
abstract: There are more than 50 subtypes of soft tissue sarcomas, among which 30% are associated with specific genetic alterations, including translocations. Several studies have reported associations between cancer risk and polymorphisms of DNA repair genes from the nucleotide excision repair (NER) pathway. NER involves more than 20 proteins whose inactivation leads to xeroderma pigmentosum (XP) or cockayne syndrome (CS), among which XPD, a helicase allowing DNA strand excision by the endonuclease XPG. DNA from 93 patients with synovial sarcomas, myxoid liposarcomas, dermatofibrosarcomas protuberans (DFSP), malignant fibrous histiocytomas and leiomyosarcomas were genotyped for both XPD Lys751Gln and XPG Asp1104His polymorphisms. Departure from Hardy-Weinberg was highly significant for the XPG polymorphism with an excess of heterozygotes in synovial sarcomas (p = 1.5 x 10(-5)), myxoid liposarcomas (p = 1.5 x 10(-4)) and to a lesser extent in DFSP (p = 0.028). In the case of XPD, a significant deviation was observed in synovial sarcomas (p = 3 x 10(-6)) and DFSP (p = 0.0014). When tumors were pooled according to their genetic alterations, the proportion of carriers of the variant XPG allele was significantly increased in sarcomas with specific translocations as compared to sarcomas with complex genetics (p < 10(-9)). No difference was found for XPD. Genotyping of the tumor samples in synovial sarcomas and myxoid liposarcomas revealed frequent loss of heterozygosity for XPG, mostly due to the loss of the frequent allele. For XPD, both alleles were lost with a similar frequency. Our results raise the potential implication of the XPG Asp1104His polymorphism in the occurrence of chromosomal translocations associated with specific subtypes of sarcomas.
authors.affiliation: Laboratory of Pharmacology of Anticancer Agents EA 515, Institut Bergonié & Université Victor Segalen Bordeaux 2, Bordeaux, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Le Morvan
authors.forename: Michel
authors.initials: M
authors.lastname: Longy
authors.forename: Catherine
authors.initials: C
authors.lastname: Bonaïti-Pellié
authors.forename: Binh
authors.initials: B
authors.lastname: Bui
authors.forename: Nadine
authors.initials: N
authors.lastname: Houédé
authors.forename: Jean-Michel
authors.initials: JM
authors.lastname: Coindre
authors.forename: Jacques
authors.initials: J
authors.lastname: Robert
authors.forename: Philippe
authors.initials: P
authors.lastname: Pourquier
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002648:Child; D004247:DNA / Q000235:genetics*; D004260:DNA Repair / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009687:Nuclear Proteins / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D012509:Sarcoma / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics*; D051760:Xeroderma Pigmentosum Group A Protein / Q000235:genetics*; D000099250:DNA Excision Repair Protein ERCC-5
chemical_list: D004247:DNA; D004268:DNA-Binding Proteins; D004720:Endonucleases; D009687:Nuclear Proteins; D014157:Transcription Factors; D051760:Xeroderma Pigmentosum Group A Protein; D000099250:DNA Excision Repair Protein ERCC-5