A t(4;22) in a meningioma points to the localization of a putative tumor-suppressor gene.
Cytogenetic analysis of meningioma cells from one particular patient (MN32) displayed the stem-line karyo-type 45, XY, -1, 4p+, 22q-, 22q+, which thus had rearrangements of both chromosomes 22. The 22q+ marker appeared as a dicentric: 22 pter----q11::1p11----qter. The reciprocal product of this translocation has presumably been lost because it lacked a centromere. The 22q- chromosome also appeared to have lost sequences distal to band q11. We assumed that this marker could have been the result of a reciprocal translocation between chromosomes 4 and 22. To investigate the 4p+ and 22q- chromosomes in more detail, human-hamster somatic cell hybrids were constructed that segregated the 22q- and 4p+ chromosomes. Southern blot analysis with DNA from these hybrids showed that sequences from 22q were indeed translocated to 4p+ and that reciprocally sequences from 4p were translocated to 22q-, demonstrating a balanced t(4;22)(p16;q11). On the basis of these results we presume that in this tumor a tumor-suppressor gene is deleted in the case of the 22q+ marker and that the t(4;22) disrupts the second allele of this gene. The latter translocation was mapped between D22S1 and D22S15, a distance of 1 cM on the linkage map of this chromosome. The area in which we have located the translocation is within the region where the gene predisposing to neurofibromatosis 2 has been mapped.
Lekanne Deprez
R H
RH
Departments of Pathology, Erasmus University, Rotterdam, The Netherlands.
Groen
N A
NA
van Biezen
N A
NA
Hagemeijer
A
A
van Drunen
E
E
Koper
J W
JW
Avezaat
C J
CJ
Bootsma
D
D
Zwarthoff
E C
EC
D000483:Alleles; D000818:Animals; D002871:Chromosome Banding; D002892:Chromosomes, Human, Pair 22 / Q000648:ultrastructure*; D002894:Chromosomes, Human, Pair 4 / Q000648:ultrastructure*; D006224:Cricetinae; D004247:DNA / Q000737:chemistry; D016147:Genes, Tumor Suppressor; D008040:Genetic Linkage; D005819:Genetic Markers; D006801:Humans; D006822:Hybrid Cells / Q000648:ultrastructure; D008579:Meningioma / Q000235:genetics*; D014178:Translocation, Genetic; D014407:Tumor Cells, Cultured
D005819:Genetic Markers; D004247:DNA