title: Chromosome 22q dosage in composite extrarenal rhabdoid tumors: clonal evolution or a phenotypic mimic?
abstract: Composite extrarenal rhabdoid tumors (CERTs) represent a diverse group of neoplasms with rhabdoid shape in combination with one of several distinctive tumor types. Like the classic renal and extrarenal malignant rhabdoid tumor (MRT), as well as the atypical teratoid/rhabdoid tumor (AT/RT) of the central nervous system, CERTs typically show aggressive clinical behavior. Deletions and mutations of the INII gene on 22q11.2 have been identified in most classic MRTs and AT/RTs; however, it is not known whether the rhabdoid components in CERTs have similar genetic abnormalities. Using fluorescence in situ hybridization (FISH) on archival, paraffin-embedded tissue with a commercially available probe in close proximity to the INII locus (bcr), as well as other chromosome 22 probes, we studied 4 cases of MRT, 13 of AT/RT, and 16 of CERT (3 melanoma, 4 meningioma, 7 carcinoma, 1 rhabdomyosarcoma, and 1 neuroblastoma). Deletion of the 22q11.2 locus was demonstrated in 10 (77%) of 13 AT/RTs and 3 (75%) of 4 MRT, including 1 congenital MRT. Of the 16 CERTs, only 2 (a rhabdoid meningioma and a carcinoma with rhabdoid features; 13%) harbored a deletion at this locus. This difference was statistically significant (P <.001). We conclude that deletion of 22q11.2, typical of most classic MRTs and AT/RTs, is infrequently seen in CERTs. This suggests that the rhabdoid component of CERTs does not evolve by way of the genetic alteration characteristic of MRTs or AT/RTs, but represents instead a distinct phenotype shared by a number of tumors as they undergo anaplastic progression.
authors.affiliation: Division of Neuropathology, Department of Pathology and Immunology, Barnes-Jewish and St Louis Children's Hospitals, Washington University Medical Center, St Louis, MO 63110, USA.
authors.forename: C E
authors.initials: CE
authors.lastname: Fuller
authors.forename: J
authors.initials: J
authors.lastname: Pfeifer
authors.forename: P
authors.initials: P
authors.lastname: Humphrey
authors.forename: L A
authors.initials: LA
authors.lastname: Bruch
authors.forename: L P
authors.initials: LP
authors.lastname: Dehner
authors.forename: A
authors.initials: A
authors.lastname: Perry
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D002675:Child, Preschool; D002874:Chromosome Mapping; D002892:Chromosomes, Human, Pair 22; D002999:Clone Cells; D005260:Female; D017353:Gene Deletion; D018628:Gene Dosage; D006801:Humans; D007150:Immunohistochemistry; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000032:analysis; D009369:Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D010641:Phenotype; D018335:Rhabdoid Tumor / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D013724:Teratoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology / Q000601:surgery
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins