Constitutional translocation t(1;17)(p36.31-p36.13;q11.2-q12.1) in a neuroblastoma patient. Establishment of somatic cell hybrids and identification of PND/A12M2 on chromosome 1 and NF1/SCYA7 on chromosome 17 as breakpoint flanking single copy markers.
Cytogenetic and molecular studies in neuroblastoma suggest the presence of a tumor suppressor gene at the distal band p36 of human chromosome 1. We described a constitutional translocation t(1;17)(p36;q12-q21), involving the critical region 1p36, in a patient with neuroblastoma, and hypothesized that the translocation predisposed the patient to tumor development. Here we report the molecular delineation of the translocation breakpoints. Somatic cell hybrids were generated by fusion of the patient's fibroblasts with the thymidine kinase deficient hamster cell line, a3. In hybrid cell lines which retained the human derivative chromosomes, the position of chromosome 1p and 17q DNA probes respective to the translocation breakpoints was determined by fluorescence in situ hybridization and Southern blot analysis. The chromosome 1p breakpoint was localized within a repetitive region encoding t-RNA genes, with 12A-2 (PND) as most distal and pHE2.6 (A12M2) as most proximal single-copy breakpoint flanking markers. For the chromosome 17 breakpoint, the proximal and distal flanking markers were identified as 7G4 (NF1) and cMCP-3 (SCYA7), respectively. In this study, cMCP-3 (SCYA7), encoding the human monocyte chemotactic protein-3, was mapped between NF1 and ERBB2. As a pivotal step towards breakpoint cloning, at present these flanking markers optimally delineate the breakpoint regions of both chromosomes 1 and 17 at the molecular level.
Laureys
G
G
Department of Pediatric Oncology, University Hospital, Ghent, Belgium.
Speleman
F
F
Versteeg
R
R
van der Drift
P
P
Chan
A
A
Leroy
J
J
Francke
U
U
Opdenakker
G
G
Van Roy
N
N
D000818:Animals; D015139:Blotting, Southern; D002874:Chromosome Mapping; D002878:Chromosomes, Human, Pair 1; D002886:Chromosomes, Human, Pair 17; D006224:Cricetinae; D003412:Cricetulus; D016147:Genes, Tumor Suppressor; D005819:Genetic Markers; D006801:Humans; D006822:Hybrid Cells; D009447:Neuroblastoma / Q000235:genetics*; D025542:Neurofibromin 1; D011506:Proteins / Q000235:genetics; D014178:Translocation, Genetic
D005819:Genetic Markers; D025542:Neurofibromin 1; D011506:Proteins