title: Sacrococcygeal chordomas in patients with tuberous sclerosis complex show somatic loss of TSC1 or TSC2.
abstract: Chordomas are rare sacrococcygeal/sacral, sphenooccipital/clivus, and spinal tumors whose molecular etiology remains relatively understudied. As several anecdotal reports had described chordomas in individuals with tuberous sclerosis complex (TSC), a multisystem hamartoma syndrome, we hypothesized that the genes that cause TSC may have an etiological role in chordomas. In two cases of sacrococcygeal chordomas in individuals with TSC, one with a germ-line TSC2 mutation and the other with a germ-line TSC1 mutation, we confirmed somatic inactivation of the corresponding wild-type allele by loss of heterozygosity analysis and immunohistochemistry. These data provide the first evidence of a pathogenic role by TSC genes in sacrococcygeal chordomas.
authors.affiliation: Tumour Molecular Genetics Group, Institute of Medical Genetics, University of Wales College of Medicine, Cardiff, UK. Lee-JonesL@Cardiff.ac.uk
authors.forename: Lisa
authors.initials: L
authors.lastname: Lee-Jones
authors.forename: Irene
authors.initials: I
authors.lastname: Aligianis
authors.forename: Peter A
authors.initials: PA
authors.lastname: Davies
authors.forename: Ana
authors.initials: A
authors.lastname: Puga
authors.forename: Peter A
authors.initials: PA
authors.lastname: Farndon
authors.forename: Anat
authors.initials: A
authors.lastname: Stemmer-Rachamimov
authors.forename: Vijaya
authors.initials: V
authors.lastname: Ramesh
authors.forename: Julian R
authors.initials: JR
authors.lastname: Sampson
mesh_terms: D002648:Child; D002817:Chordoma / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007223:Infant; D019656:Loss of Heterozygosity; D018807:Polymorphism, Single-Stranded Conformational; D011247:Pregnancy; D011506:Proteins / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics*; D012445:Sacrococcygeal Region; D014402:Tuberous Sclerosis / Q000235:genetics* / Q000503:physiopathology; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins
chemical_list: D011506:Proteins; D012097:Repressor Proteins; C000624650:TSC1 protein, human; C000624653:TSC2 protein, human; D000077004:Tuberous Sclerosis Complex 1 Protein; D000077005:Tuberous Sclerosis Complex 2 Protein; D025521:Tumor Suppressor Proteins