CONSTITUTIONAL TRANSLOCATION T(1-17)(P36.31-P36.13-Q11.2Q12.1) 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 presenc e of a tumor suppressor gene at the distal band p36 of human chromosom e 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 tum or development, Here we report the molecular delineation of the transl ocation 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 derivativ e chromosomes, the position of chromosome 1p and 17q DNA probes respec tive to the translocation breakpoints was determined by fluorescence i n situ hybridization and Southern blot analysis, The chromosome Ip bre akpoint was localized within a repetitive region encoding t-RNA genes, with 12A-2 (PND) as most distal and pHE2.6 (A12M2) as most proximal s ingle-copy breakpoint flanking markers, For the chromosome 17 breakpoi nt, the proximal and distal flanking markers were identified as 7G4 (N F1) and cMCP-3 (SCYA7), respectively, In this study, cMCP-3 (SCYA7), e ncoding the human monocyte chemotactic protein-3, was mapped between N F1 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.