title: The MDM2 SNP309 G allele is not preferentially amplified in bone and soft tissue tumors.
abstract: The transcriptional enhancer region in intron 1 of the proto-oncogene MDM2 contains a polymorphic site (SNP309) that may harbor a G or a T nucleotide. Previous studies have shown that the G allele confers a higher affinity for the Sp1 transcription factor, resulting in an increased transcriptional activity of MDM2. A constitutional G allele has also been associated with earlier onset of various cancer types, and studies of sarcomas have shown an enrichment of the G allele in tumors with MDM2 amplification, notably atypical lipomatous tumor (also known as well-differentiated liposarcoma). In the present study, we analyzed the SNP309 genotype in blood samples and tumor tissue from 57 patients with bone or soft tissue tumors showing amplification of MDM2. We did not observe any constitutional enrichment of the G allele. More importantly, there was no preferential amplification of the G allele in tumor tissue from TG heterozygotes. The expression levels of MDM2 messenger RNA were not higher in tumors with amplification of the G allele than in tumors with amplification of the T allele. Thus, we could not find any evidence for a selective advantage of the SNP309 G allele in bone and soft tissue tumors with MDM2 amplification.
authors.affiliation: Department of Clinical Genetics, University and Regional Laboratories, Skåne University Hospital, Lund University, Lund, Sweden. Frederik.mertens@med.lu.se
authors.forename: Fredrik
authors.initials: F
authors.lastname: Mertens
authors.forename: Otte
authors.initials: O
authors.lastname: Brosjö
authors.forename: Fredrik Vult
authors.initials: FV
authors.lastname: von Steyern
authors.forename: Karolin H
authors.initials: KH
authors.lastname: Nord
authors.forename: Nils
authors.initials: N
authors.lastname: Mandahl
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001859:Bone Neoplasms / Q000737:chemistry / Q000235:genetics*; D005260:Female; D005784:Gene Amplification; D006801:Humans; D008080:Liposarcoma / Q000737:chemistry / Q000235:genetics; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D000090063:Proto-Oncogene Mas; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics; D012983:Soft Tissue Neoplasms / Q000737:chemistry / Q000235:genetics*
chemical_list: C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D012333:RNA, Messenger; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2