Sacrococcygeal chordomas in patients with tuberous sclerosis complex show somatic loss of TSC1 or TSC2.
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.
Lee-Jones
Lisa
L
Tumour Molecular Genetics Group, Institute of Medical Genetics, University of Wales College of Medicine, Cardiff, UK. Lee-JonesL@Cardiff.ac.uk
Aligianis
Irene
I
Davies
Peter A
PA
Puga
Ana
A
Farndon
Peter A
PA
Stemmer-Rachamimov
Anat
A
Ramesh
Vijaya
V
Sampson
Julian R
JR
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
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