Lack of parental origin specificity of altered alleles at 11p15 in testicular germ cell tumors.
Allelic imbalance (AI) at loci on chromosome 11 has been shown in several types of human solid tumors, including testicular germ cell tumors (TGCTs). In this study we have focused on the 11p15 region, which is known for its high density of imprinted genes. Highly polymorphic microsatellite markers were analyzed in a series of 71 TGCTs, and AI was observed in 28 of the tumors (39%) at one or more of the loci analyzed. The AI data were evaluated against the chromosome 11 copy number, determined by fluorescence in situ hybridization with a centromere-specific probe. To evaluate preferential parental allele alterations, the patients' normal and tumor genotypes were compared with the parental genotypes. Both losses and gains of both paternal and maternal alleles were found, and this lack of parental origin specificity of the altered allele suggests that the remaining allele is not inactivated by imprinting. A smallest region of overlapping changes was identified between the markers D11S2351 and D11S2347. In summary, our results support the theory that a nonimprinted 11p15 tumor suppressor gene is involved in the development of a subgroup of TGCTs.
Department of Genetics, Institute for Cancer Research, The Norwegian Radium Hospital, Montebello, N-0310, Oslo, Norway.
Sigrid M
SM
Kraggerud
Maxwell P
MP
Lee
Rolf I
RI
Skotheim
Anna E
AE
Stenwig
Sophie D
SD
Fosså
Andrew P
AP
Feinberg
Ragnhild A
RA
Lothe
D000483:Alleles; D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002880:Chromosomes, Human, Pair 11; D017931:DNA Primers; D005819:Genetic Markers; D018392:Genomic Imprinting / Q000235:genetics*; D018237:Germinoma / Q000235:genetics* / Q000473:pathology; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D016133:Polymerase Chain Reaction; D013736:Testicular Neoplasms / Q000235:genetics* / Q000473:pathology
D017931:DNA Primers; D005819:Genetic Markers